Biomedical subjects

Hans A Keizer

Publications and source records attributed to Hans A Keizer.

17 recordsLinked to original sources

PubMed2006

Glycaemic instability is an underestimated problem in Type II diabetes.

The aim of the present study was to assess the level of glycaemic control by the measurement of 24 h blood glucose profiles and standard blood analyses under identical nutritional and physical activity conditions in patients with Type II diabetes and healthy normoglycaemic controls. A total of 11 male patients with Type II diabetes and 11 healthy matched controls participated in a 24 h CGMS (continuous subcutaneous glucose-monitoring system) assessment trial under strictly standardized dietary and physical activity conditions. In addition, fasting plasma glucose, insulin and HbA(1c) (glycated haemoglobin) concentrations were measured, and an OGTT (oral glucose tolerance test) was performed to calculate indices of whole-body insulin sensitivity, oral glucose tolerance and/or glycaemic control. In the healthy control group, hyperglycaemia (blood glucose concentration >10 mmol/l) was hardly present (2+/-1% or 0.4+/-0.2/24 h). However, in the patients with Type II diabetes, hyperglycaemia was experienced for as much as 55+/-7% of the time (13+/-2 h over 24 h) while using the same standardized diet. Breakfast-related hyperglycaemia contributed most (46+/-7%; P<0.01 as determined by ANOVA) to the total amount of hyperglycaemia and postprandial glycaemic instability. In the diabetes patients, blood HbA(1c) content correlated well with the duration of hyperglycaemia and the postprandial glucose responses (P<0.05). In conclusion, CGMS determinations show that standard measurements of glycaemic control underestimate the amount of hyperglycaemia prevalent during real-life conditions in Type II diabetes. Given the macro- and micro-vascular damage caused by postprandial hyperglycaemia, CGMS provides an excellent tool to evaluate alternative therapeutic strategies to reduce hyperglycaemic blood glucose excursions.

Blood Glucose↗

PubMed2006

Effects of increasing insulin secretion on acute postexercise blood glucose disposal.

BACKGROUND: Coingestion of protein and/or free amino acids with carbohydrate has been reported to accelerate postexercise muscle glycogen synthesis due to an increase in the insulin response. PURPOSE: To determine the extent to which the combined ingestion of carbohydrate and a casein protein hydrolysate with or without additional free leucine can increase insulin levels during postexercise recovery in endurance-trained athletes. To determine how this affects whole-body plasma glucose disposal during postexercise recovery. METHODS: Fourteen male athletes (age: 24.3 +/- 0.8 yr; VO2max: 62.9 +/- 1.4 mL.kg.min) were subjected to three randomized crossover trials in which they performed 2 h of exercise (55% Wmax). Thereafter, subjects were studied for 3.5 h during which they ingested carbohydrate (CHO: 0.8 g.kg.h), carbohydrate and a protein hydrolysate (CHO-PRO: 0.8 and 0.4 g.kg.h, respectively), or carbohydrate, a protein hydrolysate, and free leucine (CHO-PRO-LEU: 0.8, 0.4, and 0.1 g.kg.h, respectively) in a double-blind fashion. Continuous infusions with [6,6-H2] glucose were applied to quantify plasma glucose appearance (Ra) and disappearance rates (Rd). RESULTS: Plasma insulin responses were 108 +/- 17 and 190 +/- 33% greater in the CHO-PRO and CHO-PRO-LEU trial, respectively, compared with the CHO-trial (P < 0.01). Plasma glucose responses were lower in the CHO-PRO and CHO-PRO-LEU trial compared with the CHO-trial (35 +/- 5 and 42 +/- 11% lower, respectively; P < 0.01). Plasma glucose Ra and Rd were greater in the CHO versus the CHO-PRO and CHO-PRO-LEU trials (P < 0.05). Glucose Rd represented 100 +/- 0.03% of Ra in all trials. CONCLUSIONS: The combined ingestion of a protein hydrolysate and/or free leucine with carbohydrate (0.8 g.kg.h) substantially augments insulin secretion, but does not affect plasma glucose disposal during the first 3.5 h of postexercise recovery in trained athletes.

Adult↗

PubMed2006

Influence of acute exercise on hyperglycemia in insulin-treated type 2 diabetes.

INTRODUCTION: The impact of exercise on blood glucose homeostasis has not been assessed in long-standing type 2 diabetes patients receiving exogenous insulin treatment. PURPOSE: To study the effects of an acute bout of exercise on the subsequent 24-h blood glucose excursions under free-living conditions in insulin-treated type 2 diabetes patients. METHODS: Eleven male type 2 diabetes patients (59 +/- 2 yr) performed an acute bout of exercise. One day before the exercise bout, a continuous glucose monitoring system (GlucoDay, A. Menarini Diagnostics) was inserted subcutaneously in the periumbilical region. The glucose sensor continuously measured glucose concentrations in the dialysate during a 48-h period. RESULTS: The prevalence of hyperglycemic glucose excursions was reduced by 39% during a 24-h period (equivalent to 3 h) after an acute bout of exercise (P < 0.05). Average glucose concentrations 24 h before and after the exercise bout did not differ (NS). Mean dialysate glucose concentrations and the prevalence of hyperglycemic periods correlated strongly with baseline blood HbA1c concentrations (Pearson's R = 0.69, P < 0.05). CONCLUSION: An acute bout of exercise effectively reduces the prevalence of hyperglycemia during a 24-h period under free-living conditions in long-standing type 2 diabetes patients on exogenous insulin therapy.

Aged↗

PubMed2006

Effect of exercise on activation of the p38 mitogen-activated protein kinase pathway, c-Jun NH2 terminal kinase, and heat shock protein 27 in equine skeletal muscle.

OBJECTIVE: To investigate the effects of exercise on activation of mitogen-activated protein kinase (MAPK) signaling proteins in horses. ANIMALS: 6 young trained Standardbred geldings. PROCEDURE: Horses performed a 20-minute bout of exercise on a treadmill at 80% of maximal heart rate. Muscle biopsy specimens were obtained from the vastus lateralis and pectoralis descendens muscles before and after exercise. Amount of expression and intracellular location of phosphospecific MAPK pathway intermediates were determined by use of western blotting and immunofluorescence staining. RESULTS: Exercise resulted in a significant increase in phosphorylation of p38 pathway intermediates, c-Jun NH2 terminal kinase (JNK), and heat shock protein 27 (HSP27) in the vastus lateralis muscle, whereas no significant changes were found in phosphorylation of extracellular regulated kinase. In the pectoralis descendens muscle, phosphorylation of p38 and HSP27 was significantly increased after exercise. Immunohistochemical analysis revealed fiber-type- specific locations of phosphorylated JNK in type 2a/b intermediate and 2b fibers and phosphorylated p38 in type 1 fibers. Phosphorylated HSP27 was strongly increased after exercise in type 1 and 2a fibers. CONCLUSIONS AND CLINICAL RELEVANCE: The p38 pathway and JNK are activated in the vastus lateralis muscle after a single 20-minute bout of submaximal exercise in trained horses. Phosphorylation of HSP27 as detected in the study reported here is most likely induced through the p38 signaling pathway.

Animals↗

PubMed2005

Inhibition of adipose tissue lipolysis increases intramuscular lipid and glycogen use in vivo in humans.

This study investigates the consequences of inhibition of adipose tissue lipolysis on skeletal muscle substrate use. Ten subjects were studied at rest and during exercise and subsequent recovery under normal, fasting conditions (control trial, CON) and following administration of a nicotinic acid analog (low plasma free fatty acid trial, LFA). Continuous [U-13C]palmitate and [6,6-2H2]glucose infusions were applied to quantify plasma free fatty acid (FFA) and glucose oxidation rates and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected to measure 1) fiber type-specific IMTG content; 2) allosteric regulators of hormone-sensitive lipase (HSL), glycogen phosphorylase, and pyruvate dehydrogenase; and 3) the phosphorylation status of HSL at Ser563 and Ser565. Administration of a nicotinic acid analog (acipimox) substantially reduced plasma FFA rate of appearance and subsequent plasma FFA concentrations (P < 0.0001). At rest, this substantially reduced plasma FFA oxidation rates, which was compensated by an increase in the estimated IMTG use (P < 0.05). During exercise, the progressive increase in FFA rate of appearance, uptake, and oxidation was prevented in the LFA trial and matched by greater IMTG and glycogen use. Differential phosphorylation of HSL or relief of its allosteric inhibition by long-chain fatty acyl-CoA could not explain the increase in muscle TG use, but there was evidence to support the contention that regulation may reside at the level of the glucose-fatty acid cycle. This study confirms the hypothesis that plasma FFA availability regulates both intramuscular lipid and glycogen use in vivo in humans.

Adipose Tissue↗

PubMed2005

A single session of resistance exercise enhances insulin sensitivity for at least 24 h in healthy men.

The aim of the present study was to determine whether a single session of resistance exercise improves whole-body insulin sensitivity in healthy men for up to 24 h. Twelve male subjects (23 +/- 1 years) were studied over a period of 4 days during which they consumed a standardized diet, providing 0.16 +/- 0.01 MJ.kg(-1).day(-1) containing 15 +/- 0.1 energy% (En%) protein, 29 +/ -0.1 En% fat and 55 +/- 0.3 En% carbohydrate. Insulin sensitivity was determined 24 h before and 24 h after a single resistance exercise session (8 sets of 10 repetitions at 75% of 1 repetition maximum for two leg exercise tasks) using an intravenous insulin tolerance test. Insulin sensitivity index was calculated by the decline in arterial blood glucose concentration following intravenous administration of a single bolus of human insulin (0.075 IU.kg(-1) fat free mass). Basal glucose and insulin concentrations were not changed up to 24 h after the resistance exercise. However, a substantial 13+/-5% improvement in whole-body insulin sensitivity was observed, 24 h after the resistance exercise (P < 0.05). This study shows that even a single session of resistance exercise improves whole-body insulin sensitivity for up to 24 h in healthy men, which is consistent with earlier observations following endurance exercise tasks.

Adaptation, Physiological↗

PubMed2005

The effects of exercise and adipose tissue lipolysis on plasma adiponectin concentration and adiponectin receptor expression in human skeletal muscle.

OBJECTIVE: It has been suggested that adiponectin regulates plasma free fatty acid (FFA) clearance by stimulating FFA uptake and/or oxidation in muscle. We aimed to determine changes in plasma adiponectin concentration and adiponectin receptor 1 and 2 mRNA expression in skeletal muscle during and after prolonged exercise under normal, fasting conditions (high FFA trial; HFA) and following pharmacological inhibition of adipose tissue lipolysis (low FFA trial; LFA). Furthermore, we aimed to detect and locate adiponectin in skeletal muscle tissue. METHODS: Ten subjects performed two exercise trials (120 min at 50% VO(2max)). Indirect calorimetry was used to determine total fat oxidation rate. Plasma samples were collected at rest, during exercise and during post-exercise recovery to determine adiponectin, FFA and glycerol concentrations. Muscle biopsies were taken to determine adiponectin protein and adiponectin receptor 1 and 2 mRNA expression and to localise intramyocellular adiponectin. RESULTS: Basal plasma adiponectin concentrations averaged 6.57+/-0.7 and 6.63+/-0.8 mg/l in the HFA and LFA trials respectively, and did not change significantly during or after exercise. In the LFA trial, plasma FFA concentrations and total fat oxidation rates were substantially reduced. However, plasma adiponectin and muscle adiponectin receptor 1 and 2 mRNA expression did not differ between trials. Immunohistochemical staining of muscle cross-sections showed the presence of adiponectin in the sarcolemma of individual muscle fibres and within the interfibrillar arterioles. CONCLUSION: Plasma adiponectin concentrations and adiponectin receptor 1 and 2 mRNA expression in muscle are not acutely regulated by changes in adipose tissue lipolysis and/or plasma FFA concentrations. Adiponectin is abundantly expressed in muscle, and, for the first time, it has been shown to be present in/on the sarcolemma of individual muscle fibres.

Adiponectin↗

PubMed2005

Effects of short- and long-term recombinant equine growth hormone and short-term hydrocortisone administration on tissue sensitivity to insulin in horses.

OBJECTIVE: To determine the effects of short-term IV administration of hydrocortisone or equine growth hormone (eGH) or long-term IM administration of eGH to horses on tissue sensitivity to exogenous insulin. ANIMALS: 5 Standardbreds and 4 Dutch Warmblood horses. PROCEDURE: The euglycemic-hyperinsulinemic clamp technique was used to examine sensitivity of peripheral tissues to exogenous insulin 24 hours after administration of a single dose of hydrocortisone (0.06 mg/kg), eGH (20 microg/kg), or saline (0.9% NaCl) solution and after long-term administration (11 to 15 days) of eGH to horses. The amounts of metabolized glucose (M) and plasma insulin concentration (I) were determined. RESULTS: Values for M and the M-to-I ratio were significantly higher 24 hours after administration of a single dose of hydrocortisone than after single-dose administration of eGH or saline solution. After long-term administration of eGH, basal I concentration was increased and the mean M-to-I ratio was 22% lower, compared with values for horses treated with saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: Increases in M and the M-to-I ratio after a single dose of hydrocortisone imply that short-term hydrocortisone treatment increases glucose use by, and insulin sensitivity of, peripheral tissues. Assuming a single dose of hydrocortisone improves sensitivity of peripheral tissues to insulin, it may be an interesting candidate for use in reducing insulin resistance in peripheral tissues of horses with several disease states. In contrast, long-term administration of eGH decreased tissue sensitivity to exogenous insulin associated with hyperinsulinemia. Therefore, increased concentrations of growth hormone may contribute to insulin resistance in horses with various disease states.

3-Hydroxybutyric Acid↗

PubMed2004

Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects.

The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of L-[ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 +/- 19% and +77 +/- 11%, respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial (P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials (P < 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 +/- 0.006 vs. 0.061 +/- 0.008%/h, respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 +/- 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.

Adult↗

PubMed2004

A modified PAS stain combined with immunofluorescence for quantitative analyses of glycogen in muscle sections.

Simultaneous analyses of glycogen in sections with other subcellular constituents within the same section will provide detailed information on glycogen deposition and the processes involved. To date, staining protocols for quantitative glycogen analyses together with immunofluorescence in the same section are lacking. We aimed to: (1) optimise PAS staining for combination with immunofluorescence, (2) perform quantitative glycogen analyses in tissue sections, (3) evaluate the effect of section thickness on PAS-derived data and (4) examine if semiquantitative glycogen data were convertible to genuine glycogen values. Conventional PAS was successfully modified for combined use with immunofluorescence. Transmitted light microscopic examination of glycogen was successfully followed by semiquantification of glycogen using microdensitometry. Semiquantitative data correlated perfectly with glycogen content measured biochemically in the same sample (r2=0.993, P<0.001). Using a calibration curve (r2=0.945, P<0.001) derived from a custom-made external standard with incremental glycogen content, we converted the semiquantitative data to genuine glycogen values. The converted semiquantitative data were comparable with the glycogen values assessed biochemically (P=0.786). In addition we showed that for valid comparison of glycogen content between sections, thickness should remain constant. In conclusion, the novel protocol permits the combined use of PAS with immunofluorescence and shows valid conversion of data obtained by microdensitometry to genuine glycogen data.

Adult↗

PubMed2004

Intramyocellular lipid content in type 2 diabetes patients compared with overweight sedentary men and highly trained endurance athletes.

Recent evidence suggests that intramyocellular lipid (IMCL) accretion is associated with obesity and the development of insulin resistance and/or type 2 diabetes. However, trained endurance athletes are markedly insulin sensitive, despite an elevated mixed muscle lipid content. In an effort to explain this metabolic paradox, we compared muscle fiber type-specific IMCL storage between populations known to have elevated IMCL deposits. Immunofluorescence microscopy was performed on muscle biopsies obtained from eight highly trained endurance athletes, eight type 2 diabetes patients, and eight overweight, sedentary men after an overnight fast. Mixed muscle lipid content was substantially greater in the endurance athletes (4.0 +/- 0.4% area lipid stained) compared with the diabetes patients and the overweight men (2.3 +/- 0.4 and 2.2 +/- 0.5%, respectively). More than 40% of the greater mixed muscle lipid content was attributed to a higher proportion type I muscle fibers (62 +/- 8 vs. 38 +/- 3 and 33 +/- 7%, respectively), which contained 2.8 +/- 0.3-fold more lipid than the type II fibers. The remaining difference was explained by a significantly greater IMCL content in the type I muscle fibers of the trained athletes. Differences in IMCL content between groups or fiber types were accounted for by differences in lipid droplet density, not lipid droplet size. IMCL distribution showed an exponential increase in lipid content from the central region toward the sarcolemma, which was similar between groups and fiber types. In conclusion, IMCL contents can be substantially greater in trained endurance athletes compared with overweight and/or type 2 diabetes patients. Because structural characteristics and intramyocellular distribution of lipid aggregates seem to be similar between groups, we conclude that elevated IMCL deposits are unlikely to be directly responsible for inducing insulin resistance.

Adult↗

PubMed2004

Subcellular immunolocalisation of fatty acid translocase (FAT)/CD36 in human type-1 and type-2 skeletal muscle fibres.

Limited information exists about the putative role and expression in human skeletal muscle cells of the 88-kDa integral membrane protein fatty acid translocase (FAT), highly homologous to the human leucocyte differentiation factor CD36. Therefore, we investigated in healthy male individuals the muscle (m. vastus lateralis) fibre type specific expression and subcellular localisation of FAT/CD36. For this purpose four different monoclonal antibodies raised against human and mouse FAT/CD36 were used. Acetone or methanol/acetone fixation were tested. Serial cryosections were cut at -20 degrees C, thaw-mounted on uncoated glass slides and air-dried before processing indirect immunofluorescence assays. Images were examined in a Nikon ER800 microscope, digitally captured, processed and analysed by LUCIA laboratory software. Three antibodies showed that FAT/CD36 was: (1) most abundantly expressed in capillary endothelium, (2) colocalised with caveolin-3, which indicates that FAT/CD36 is in the sarcolemma, or its close vicinity, and (3) abundantly expressed in (or in the close vicinity) of the sarcolemma and intracellular structures of type-1 muscle fibres, and much less abundantly in the sarcolemma of type-2 muscle fibres. One of the antibodies raised against mouse CD36 also detected myosin heavy chain 1, which makes it unsuitable in skeletal muscle research. The fixation (acetone or methanol/acetone) was found to be highly important for the result.

Adult↗

PubMed2004

Immunohistochemical identification and fiber type specific localization of protein kinase C isoforms in equine skeletal muscle.

OBJECTIVE: To investigate whether protein kinase C (PKC) isoforms are expressed in equine skeletal muscle and determine their distribution in various types of fibers by use of immunofluorescence microscopy. ANIMALS: 5 healthy adult Dutch Warmblood horses. PROCEDURE: In each horse, 2 biopsy specimens were obtained from the vastus lateralis muscle. Cryosections of equine muscle were stained with PKC isoform (alpha, beta1, beta2, delta, epsilon, or zeta)-specific polyclonal antibodies and examined by use of a fluorescence microscope. Homogenized muscle samples were evaluated via western blot analysis. RESULTS: The PKC alpha, beta1, beta2, delta, epsilon, and zeta isoforms were localized within the fibers of equine skeletal muscle. In addition, PKC alpha and beta2 were detected near or in the plasma membrane of muscle cells. For some PKC isoforms, distribution was specific for fiber type. Staining of cell membranes for PKC alpha was observed predominantly in fibers that reacted positively with myosin heavy chain (MHC)-IIa; PKC delta and epsilon staining were more pronounced in MHC-I-positive fibers. In contrast, MHC-I negative fibers contained more PKC zeta than MHC-I-positive fibers. Distribution of PKC beta1 was equal among the different fiber types. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that PKC isoforms are expressed in equine skeletal muscle in a fiber type-specific manner. Therefore, the involvement of PKC isoforms in signal transduction in equine skeletal muscle might be dependent on fiber type.

Animals↗

PubMed2004

Investigation of the expression and localization of glucose transporter 4 and fatty acid translocase/CD36 in equine skeletal muscle.

OBJECTIVE: To investigate the expression and localization of glucose transporter 4 (GLUT4) and fatty acid translocase (FAT/CD36) in equine skeletal muscle. SAMPLE POPULATION: Muscle biopsy specimens obtained from 5 healthy Dutch Warmblood horses. PROCEDURES: Percutaneous biopsy specimens were obtained from the vastus lateralis, pectoralis descendens, and triceps brachii muscles. Cryosections were stained with combinations of GLUT4 and myosin heavy chain (MHC) specific antibodies or FAT/CD36 and MHC antibodies to assess the fiber specific expression of GLUT4 and FAT/CD36 in equine skeletal muscle via indirect immunofluorescent microscopy. RESULTS: Immunofluorescent staining revealed that GLUT4 was predominantly expressed in the cytosol of fast type 2B fibers of equine skeletal muscle, although several type 1 fibers in the vastus lateralis muscle were positive for GLUT4. In all muscle fibers examined microscopically, FAT/CD36 was strongly expressed in the sarcolemma and capillaries. Type 1 muscle fibers also expressed small intracellular amounts of FAT/CD36, but no intracellular FAT/CD36 expression was detected in type 2 fibers. CONCLUSIONS AND CLINICAL RELEVANCE: In equine skeletal muscle, GLUT4 and FAT/CD36 are expressed in a fiber type selective manner.

Animals↗

PubMed2003

Intramyocellular lipids form an important substrate source during moderate intensity exercise in endurance-trained males in a fasted state.

Both stable isotope methodology and fluorescence microscopy were applied to define the use of intramuscular triglyceride (IMTG) stores as a substrate source during exercise on a whole-body as well as on a fibre type-specific intramyocellular level in trained male cyclists. Following an overnight fast, eight subjects were studied at rest, during 120 min of moderate intensity exercise (60 % maximal oxygen uptake capacity (VO2,max)) and 120 min of post-exercise recovery. Continuous infusions of [U-13C]palmitate and [6,6-2H2]glucose were administered at rest and during subsequent exercise to quantify whole-body plasma free fatty acid (FFA) and glucose oxidation rates and the contribution of other fat sources (sum of muscle- plus lipoprotein-derived TG) and muscle glycogen to total energy expenditure. Fibre type-specific intramyocellular lipid content was determined in muscle biopsy samples collected before, immediately after and 2 h after exercise. At rest, fat oxidation provided 66 +/- 5 % of total energy expenditure, with FFA and other fat sources contributing 48 +/- 6 and 17 +/- 3 %, respectively. FFA oxidation rates increased during exercise, and correlated well with the change in plasma FFA concentrations. Both the use of other fat sources and muscle glycogen declined with the duration of exercise, whereas plasma glucose production and utilisation increased (P < 0.001). On average, FFA, other fat sources, plasma glucose and muscle glycogen contributed 28 +/- 3, 15 +/- 2, 12 +/- 1 and 45 +/- 4 % to total energy expenditure during exercise, respectively. Fluorescence microscopy revealed a 62 +/- 7 % net decline in muscle lipid content following exercise in the type I fibres only, with no subsequent change during recovery. We conclude that IMTG stores form an important substrate source during moderate intensity exercise in endurance-trained male athletes following an overnight fast, with the oxidation rate of muscle- plus lipoprotein-derived TG being decreased with the duration of exercise.

Acetates↗

PubMed2003

Amino acid ingestion strongly enhances insulin secretion in patients with long-term type 2 diabetes.

OBJECTIVE: Insulin secretion in response to carbohydrate intake is blunted in type 2 diabetic patients. However, it is not clear whether the insulin response to other stimuli, such as amino acids, is also diminished. Recently, we defined an optimal insulinoptropic mixture containing free leucine, phenylalanine, and a protein hydrolysate that substantially enhances the insulin response in healthy young subjects when coingested with carbohydrate. In this study, we aimed to investigate the insulinotropic capacity of this mixture in long-term type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Ten type 2 diabetic patients (aged 59.1 +/- 2.0 years, BMI 26.5 +/- 0.7 kg/m(2)) and 10 healthy control subjects (58.8 +/- 2.1 years, 26.5 +/- 0.7 kg/m(2)) visited our lab twice, during which insulin responses were determined following ingestion of carbohydrate only (CHO) or carbohydrate with the free amino acid/protein mixture (CHO+PRO). All subjects received 0.7 g x kg(-1) x h(-1) carbohydrate with or without 0.35 g x kg(-1) x h(-1) of the amino acid/protein mixture. RESULTS: Insulin responses were dramatically increased in the CHO+PRO trial in both the type 2 diabetic and control groups (189 and 114%, respectively) compared with the CHO trial (P < 0.01). Plasma glucose, glucagon, growth hormone, cortisol, IGF-I, and IGF binding protein 3 responses were not different between trials within the 2-h time frame. CONCLUSIONS: The insulin secretory capacity in long-term type 2 diabetic patients is substantially underestimated, as the insulin response following carbohydrate intake can be nearly tripled by coingestion of a free amino acid/protein mixture. Future research should be performed to investigate whether such nutritional interventions can improve postprandial glucose disposal.

Amino Acids↗

PubMed2002

Evidence of insulin resistant lipid metabolism in adipose tissue in familial combined hyperlipidemia, but not type 2 diabetes mellitus.

In patients with familial combined hyperlipidemia (FCHL) and type 2 diabetes (DM2) organ-specific differences in insulin resistance may exist. In FCHL and DM2 in vivo insulin mediated muscle glucose uptake and inhibition of lipolysis were studied by euglycemic hyperinsulinemic clamp. Insulin mediated glucose uptake was impaired to the same extent in both FCHL and DM2. Only FCHL subjects showed no reduction in plasma glycerol concentrations during insulin infusion and incomplete suppression of plasma free fatty acid (FFA) concentrations combined. This finding indicated that insulin-induced suppression of lipolysis, or glycerol/FFA utilization, or both, were impaired in FCHL, in contrast to DM2 or control subjects. To analyze these possibilities in more detail, control, FCHL, and DM2 adipocytes were studied in vitro. In contrast to adipocytes from DM2 or control subjects, no reduction in medium FFA concentration was detected with FCHL adipocytes after incubation with insulin. This finding indicated impaired intracellular FFA utilization, most likely impaired FFA re-esterification. Genetic linkage analysis in 18 Dutch families with FCHL revealed no evidence for involvement of LIPE, the hormone sensitive lipase gene, indicating that genetic variation in adipocyte lipolysis by LIPE is not the key defect in FCHL. In conclusion, FCHL as well as DM2 subjects exhibited in vivo insulin resistance to glucose disposal, which occurs mainly in muscle. FCHL subjects showed insulin resistant adipose tissue lipid metabolism, in contrast to DM2 and controls. The different pattern of organ-specific insulin resistance in FCHL versus DM2 advances our understanding of differences and similarities in phenotypes between these disorders.

Adipocytes↗