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Biomedical subjects

I Lager

Publications and source records attributed to I Lager.

At least 19 recordsLinked to original sources
PubMed2005

Development and use of fluorescent nanosensors for metabolite imaging in living cells.

To understand metabolic networks, fluxes and regulation, it is crucial to be able to determine the cellular and subcellular levels of metabolites. Methods such as PET and NMR imaging have provided us with the possibility of studying metabolic processes in living organisms. However, at present these technologies do not permit measuring at the subcellular level. The cameleon, a fluorescence resonance energy transfer (FRET)-based nanosensor uses the ability of the calcium-bound form of calmodulin to interact with calmodulin binding polypeptides to turn the corresponding dramatic conformational change into a change in resonance energy transfer between two fluorescent proteins attached to the fusion protein. The cameleon and its derivatives were successfully used to follow calcium changes in real time not only in isolated cells, but also in living organisms. To provide a set of tools for real-time measurements of metabolite levels with subcellular resolution, protein-based nanosensors for various metabolites were developed. The metabolite nanosensors consist of two variants of the green fluorescent protein fused to bacterial periplasmic binding proteins. Different from the cameleon, a conformational change in the binding protein is directly detected as a change in FRET efficiency. The prototypes are able to detect various carbohydrates such as ribose, glucose and maltose as purified proteins in vitro. The nanosensors can be expressed in yeast and in mammalian cell cultures and were used to determine carbohydrate homeostasis in living cells with subcellular resolution. One future goal is to expand the set of sensors to cover a wider spectrum of metabolites by using the natural spectrum of bacterial periplasmic binding proteins and by computational design of the binding pockets of the prototype sensors.

Cells↗
PubMed2001

Long-term glycaemic improvement after addition of metformin to insulin in insulin-treated obese type 2 diabetes patients.

AIM: To assess the adjunct effect of metformin to insulin in type 2 diabetes. METHODS: Obese and overweight type 2 diabetes patients treated with insulin for at least 1 year, and with poor glycaemic control (HbA1c > upper reference level + 2%), were included in a randomised, double-blind, placebo-controlled study. Patients were treated for 12 months with either metformin (850 mg b.i.d.) or placebo added to their usual insulin, which was stabilized during a 3-month placebo run-in period, but thereafter attempted to be unchanged. RESULTS: Thirty-seven patients were included. Two patients dropped out during run-in. There were no differences between the metformin (n = 16) and placebo (n = 19) group at baseline. Most patients received multiple insulin injections. Metabolic control was improved by addition of metformin. Mean change in HbA1c from baseline showed highly significant difference between groups at 3, 6, 9 and 12 months. Mean change (percentage units +/- s.d.) at 12 months was -1.1 +/- 0.7% vs. + 0.3 +/- 0.8% (p < 0.001) for HbA1c and -1.4 +/- 2.1 mmol/l vs. + 0.6 +/- 2.2 mmol/l (p = 0.025) for fasting blood glucose. Mean low density lipoprotein (LDL) cholesterol change differed slightly at 6 months, but not at 12 months. There were no changes in insulin dose, blood pressure, body weight, triglycerides, total- and high density lipoprotein (HDL) cholesterol, fibrinogen, C-peptide and laboratory safety variables, including serum B12. Combination therapy was well-tolerated with the same adverse event rate as insulin alone, but more patients with diarrhoea. CONCLUSION: Addition of metformin to insulin induced and maintained clinically significant and consistent long-term reduction of hyperglycaemia in obese, insulin-treated type 2 diabetes patients.

Blood Glucose↗
PubMed2001

Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study.

AIMS: To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes. METHODS: Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40-75 years, body mass index (BMI) 20-35 kg/m2, HbA1c 4.2-12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1-4 mg at mealtimes, or glipizide, 5-15 mg daily. RESULTS: Changes in fasting blood glucose (FBG) and HbA1c during the 12 months of treatment showed a significant difference in favour of repaglinide. In oral hypoglycaemic agents (OHA)-naive patients, HbA1c decreased in the repaglinide and glipizide groups by 1.5% and 0.3%, respectively (P < 0.05 between groups). Fasting blood glucose decreased in the repaglinide group by 2.4 mmol/l and increased in the glipizide group by 1.0 mmol/l (P < 0.05 between groups). In the study population as a whole, repaglinide was able to maintain glycaemic control (HbA1c level) during the 1-year study period, whereas control deteriorated significantly with glipizide. Change in HbA1c from baseline was significantly better with repaglinide than with glipizide after 12 months (P < 0.05). In addition, FBG deteriorated significantly in the glipizide group compared with the repaglinide group (P < 0.05). No patients in either group experienced a major hypoglycaemic event; the number of patients experiencing minor hypoglycaemia was similar in the repaglinide and glipizide groups (15% and 19%, respectively). CONCLUSIONS: Repaglinide, given as a prandial glucose regulator, is shown to be an effective and safe treatment of patients with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients.

Adult↗
PubMed1999

Socio-economic characteristics and quality of life in diabetes mellitus--relation to metabolic control.

Diabetes mellitus is a chronic metabolic disease with wide implications for well-being and social life. The aim of this cross-sectional, observational study was to describe possible differences in clinical characteristics, socio-economic factors and quality of life between diabetes patients in poor and good/acceptable metabolic control, as defined by levels of glycated haemoglobin A1c. From a population-based register of diabetes patients at a clinical chemistry department, we selected 96 subjects in poor metabolic control (HbA1c > 10%), and 96 subjects in good/acceptable (HbA1c 6.5-7.5%) metabolic control, matched for sex, age and duration of diabetes. Each participant was sent a self-administered questionnaire regarding medical history, family situation and socio-economic background, as well as self-rated health based on a validated instrument (SF-36). The diabetes patients in poor metabolic control reported more retinopathy, vascular complications and nervous problems than did the patients in acceptable metabolic control. Furthermore, the group in poor metabolic control was also characterized by a lower educational level, a higher number of sick leave days or disability pension and a lower degree of physical activity. Both of the diabetic groups reported lower scorings for physical functioning, general health, vitality and mental health, than did a comparable non-diabetic group from another study. In summary, diabetic patients in poor metabolic control have a lower educational level and report more complications, nervous problems, sick leave days and disability pensions than patients in good/acceptable metabolic control. The lower degree of physical activity adds to the problems of the first group and should be the target for intervention to achieve better metabolic control.

Adolescent↗
PubMed1995

Growth hormone-deficient adults are insulin-resistant.

Patients with growth hormone deficiency (GHD) have traditionally been described as having increased insulin sensitivity with a tendency toward fasting hypoglycemia, at least in children. In other studies, impaired glucose tolerance has been found. To evaluate basal insulin sensitivity, a hyperinsulinemic, normoglycemic clamp was performed with an insulin rate of 40 mU/m2/min after an overnight fast. Fifteen patients (four women and 11 men aged 20 to 62 years) with GHD for at least 1 year were compared with 15 healthy controls matched for sex, age, and body mass index (BMI). Thirteen patients had complete pituitary deficiency and were being treated with conventional hormone replacement therapy. Two men had isolated GHD since childhood. Four men were being treated with bromocriptin. There were no significant differences between fasting blood glucose (4.4 +/- 0.1 v 4.7 +/- 0.2 [mean +/- SEM] mmol/L) or fasting plasma insulin (9.5 +/- 1.4 v 8.8 +/- 1.1 mU/L) in patients and controls, respectively. Fasting free fatty acid (FFA) levels were lower in patients (444 +/- 35 v 796 +/- 94 mumol/L, P < .01). Blood glucose levels during the clamp were similar (4.6 +/- 0.1 v 4.9 +/- 0.1 mmol/L), as were insulin levels (81 +/- 4 v 93 +/- 4 mU/L). A decrease in glucose infusion rate (GIR) was seen during the clamp in GHD subjects (3.9 +/- 0.5 v 9.9 +/- 0.7 mg/kg body weight/min) as compared with controls (P = .001). Even if corrections were made for body fat, there was a significant difference (GIR corrected per lean body mass, 5.8 +/- 0.8 v 13.9 +/- 0.9 mg/kg lean body mass/min, P < .001). The results suggest that adults with GHD are insulin-resistant. Despite this finding, normal fasting plasma insulin levels were seen.

Adult↗
PubMed1995

Characterization of the insulin-antagonistic effect of growth hormone in insulin-dependent diabetes mellitus.

To characterize its insulin-antagonistic effect, growth hormone (GH) was infused at variable rates (24, 12 or 6 mU kg-1 min-1) for 1 h in 7 IDDM patients. Saline infusion was used as control (C) and all patients participated in all studies. The effect of insulin was measured with the euglycaemic clamp technique for 6 h combined with d-(3-3H)-glucose to evaluate glucose turnover. The insulin levels during the clamps were similar in all studies (23 +/- 3 mU l-1). The infusions produced peak GH levels of (24 rate = 24) 157 +/- 11, (12 rate = 12) 76 +/- 7, and (6 rate = 6) 45 +/- 8 mU l-1 (mean +/- SEM). The insulin-antagonistic effect of GH on glucose uptake was seen after 2 h and was at a maximum 4 to 5 h after the start of the GH infusion (difference in glucose infusion rate between C and 24 was 1.7 +/- 0.4 mg kg-1 min-1, p < 0.01). The resistance was due to a less pronounced effect of insulin to both inhibit rate of appearance and to stimulate rate of disappearance. Infusion of GH at 12 mU kg-1 min-1 induced a less pronounced insulin resistance both with regards to maximal effect (glucose infusion rate C - GH 1.4 +/- 0.5 mg kg-1 min-1, p < 0.05) and duration (3 h). At 6 mU kg-1 min-1, a clear GH-induced insulin-antagonistic effect was only seen during the third hour of the clamp (glucose infusion rate C-GH 1.3 +/- 0.5 mg kg-1 min-1, p < 0.05). GH infusion impaired the effect of insulin to lower both the levels of free fatty acids (NEFA) and glycerol between 2 and 5 h after the start of the infusion (NEFA, C:110 +/- 29, 24:303 +/- 95, p < 0.05: glycerol, C:32 +/- 4, 24:50 +/- 7 mumol l-1, p < 0.05). The present study therefore demonstrates that the insulin-antagonistic effect of GH in IDDM is related to the plasma levels both with regard to duration and response. The results also indicate that GH impairs the effect of insulin on lipolysis in IDDM after physiological peaks.

Adult↗
PubMed1994

Regulation of insulin-like growth factor binding protein-1 (IGFBP-1) in insulin-dependent diabetes mellitus. Effects of hyperglycaemia and insulin.

The aim of the present study was to characterize the effect of 44 h of hyperglycaemia on diurnal levels of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-1 (IGF-1), growth hormone (GH) and glucagon in 7 well-controlled subjects with insulin-dependent diabetes mellitus (IDDM). Hyperglycaemia (approximately 15 mmol/l) was induced by a glucose infusion, while the degree of insulinisation was similar to that of a corresponding period with near normoglycaemia (approximately 6.9 mmol/l). Hyperglycaemia for 44 h did not alter the normal diurnal IGFBP-1 levels when the degree of insulinisation was unchanged. The diurnal secretion pattern of IGFBP-1 was preserved in both genders and without any difference between the control and hyperglycaemic periods. However, the IGFBP-1 levels were increased in these IDDM subjects despite a peripheral hyperinsulinemia. An inverse correlation was found between IGFBP-1 and peripheral insulin levels both during periods of rapid changes in IGFBP-1 and insulin concentrations (i.e. morning hours) as well as during the total 24-h sampling period. Total IGF-1 levels were low, but no further decrease was seen after 24 h of hyperglycaemia in the presence of unchanged insulin levels. In conclusion, the present study clearly shows that the increased IGFBP-1 level seen during poor metabolic control in IDDM is not caused by hyperglycaemia. Glucose levels per se do not influence either total IGF-1 or IGFBP-1 concentrations in well-insulinised diabetic patients.

Adult↗
PubMed1993

Effect of prolonged hyperglycemia on growth hormone levels and insulin sensitivity in insulin-dependent diabetes mellitus.

The aim of the present study was to characterize the effect of a hyperglycemic period (44 hours) on the levels of insulin-antagonistic hormones and insulin sensitivity in seven subjects with well-controlled insulin-dependent diabetes mellitus (IDDM). Hyperglycemia (approximately 15 mmol.L-1) was induced by a glucose infusion while the degree of insulinization was similar to that of the period with near normoglycemia (approximately 6.9 mmol.L-1). Insulin sensitivity was measured with hyperinsulinemic euglycemic clamps performed 4 hours before and after the periods of normoglycemia (control) and hyperglycemia. D-[3-3H]glucose was infused in the second clamp in each study to evaluate glucose production and utilization. Since growth hormone (GH) levels frequently are elevated during poor diabetic control, diurnal GH secretion was measured in blood samples continuously drawn for 24 hours during the euglycemic and hyperglycemic periods. Levels of epinephrine, norepinephrine, cortisol, and nonesterified free fatty acids (NEFA) were similar during the control and hyperglycemic periods and during the clamps. GH levels were also similar, but an abnormal diurnal secretion pattern was present with increased numbers of daytime peaks. Hyperglycemia did not reduce GH secretion in IDDM. Hyperglycemia for 44 hours induced insulin resistance (32% reduction of glucose infusion rate, P < .02). In the control study, a 21% reduction (P = .064, NS) of the glucose disposal rate (Rd) was seen, suggesting that the hospitalization period per se may also reduce insulin sensitivity. In conclusion, a period of hyperglycemia leads to insulin resistance in IDDM patients. This insulin resistance cannot be attributable to increased levels of insulin-antagonistic hormones, although an abnormal secretion pattern for GH was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effects of treatment with recombinant human growth hormone on insulin sensitivity and glucose metabolism in adults with growth hormone deficiency.

In a double-blind, cross-over, placebo-controlled trial, the effect of 26 weeks of replacement therapy with recombinant human growth hormone (rhGH) on insulin sensitivity and glucose metabolism in nine patients with adult-onset growth hormone deficiency was studied with a euglycemic clamp. Glucose production and utilization were studied with D-(3-3H)-glucose infusions. Comparisons were made with placebo treatment for 6 and 26 weeks, respectively. GH therapy for 6 weeks increased fasting plasma concentrations of glucose and insulin. However, after 26 weeks of GH treatment, no significant changes in glucose or insulin concentrations were recorded. GH treatment induced a marked change in insulin action evident after 6 weeks of therapy as shown by lower glucose infusion rates (GIRs) during the clamp compared with placebo treatment (2.6 +/- 0.4 v 4.1 +/- 0.7 mg.kg-1.min-1). This change in insulin action was due to a decreased insulin effect on glucose utilization. After 26 weeks of GH therapy, there was no significant difference in GIRs. During placebo treatment, insulin sensitivity and insulin, glucose, and nonesterified fatty acid (NEFA) concentrations were unchanged compared with concentrations measured before the study. Thus GH replacement therapy induces a change in insulin action in GH-deficient individuals. Whether this change represents a decrease in insulin action (ie, insulin resistance) or a restoration of action to normal is presently unclear, since a healthy control group was not included in the study. During long-term treatment, the present study suggests that the change in insulin action can be reversed, probably secondarily to changes in body composition.

Adult↗
PubMed1993

Smoking induces insulin resistance--a potential link with the insulin resistance syndrome.

OBJECTIVES: The acute effect of smoking and snuffing on insulin sensitivity was studied in a group of healthy habitual smokers. DESIGN: The euglycaemic clamp technique was combined with the subcutaneous injection of a bolus (0.1 U kg-1) of fast-acting insulin (Actrapid). Randomized subjects smoked either one cigarette per hour for 6 h, took one bag-packed snuff per hour for 6 h or refrained from nicotine for 48 h before as well as during the clamp. SUBJECTS: Seven healthy smokers, four females and three males, of normal weight (BMI, mean +/- SEM, 21 +/- 0.7 kg m-2 with a range of 18.6-23.9), aged 31 +/- 2 years (range 24-35 years), who had consumed at least 20 cigarettes per day for at least 5 years were studied. They were recruited through an advertisement in a newspaper. RESULTS: The steady-state plasma nicotine levels were similar during smoking and snuffing. The insulin and glucose levels were also similar during all three clamps. Smoking, but not snuffing, impaired insulin action (P < 0.05) mainly due to a lower peripheral glucose uptake. The mean growth hormone levels during the 6-h study were more than doubled during smoking (P < 0.01) while no significant differences were seen in the other counter-regulatory hormones. CONCLUSION: Smoking (also in habitual smokers) acutely impairs insulin action and leads to insulin resistance. Thus, smoking can be of importance for the development of the insulin resistance syndrome associated with risk for cardiovascular disease.

Adult↗
PubMed1992

Insulin-antagonistic effects of pulsatile and continuous glucagon infusions in man--a comparison with the effect of adrenaline.

The insulin-antagonistic effects of pulsatile (3 min pulses every 20 min) and continuous glucagon infusions were studied over 4 h with the euglycemic clamp technique in healthy subjects. Comparisons were made to the effect of a continuous adrenaline infusion. Glucose production and utilization were evaluated with D-3-3H-glucose and somatostatin was used in all studies to inhibit the endogenous release of insulin and glucagon. The amount of glucagon given during the pulsatile infusions (27% of that during continuous infusion) was adjusted so that the peak glucagon levels were the same as during the continuous infusion (372 +/- 22 and 365 +/- 20 ng/L, respectively). The insulin-antagonistic effects of pulsatile and continuous glucagon infusions were similar during the first hour and imparied the insulin effect with 44 +/- 8 and 47 +/- 6%, respectively. However, when infused continuously, the effect of glucagon declined rapidly, whereas the effect of a pulsatile infusion decreased more slowly and was evident for 3 h. Raising the glucagon level 4-fold restored the insulin-antagonistic effect again suggesting that the cells had become desensitized. In contrast, the insulin-antagonistic effect of adrenaline was persistent throughout the 4 h of the study and impaired insulin action with 54 +/- 2%. The effects of pulsatile and continuous glucagon infusions were entirely due to the stimulation of glucose production while that of adrenaline mainly was due to inhibition of peripheral glucose uptake. In conclusion, the acute stimulatory effect of glucagon on glucose production is transient but it is better maintained when given as intermittent pulses rather than as a continuous infusion. In contrast, the insulin-antagonistic effect of adrenaline on glucose uptake is persistent for at least 4 h.

Adult↗
PubMed1991

Characterization of the insulin-antagonistic effect of growth hormone in man.

The insulin-antagonistic effect of growth hormone was characterized by infusing the hormone at three different infusion rates (6, 12 or 24 mU.kg-1.min-1) for one h in 11 healthy subjects. The insulin effect was measured with the euglycaemic clamp technique combined with D-(3-3H)-glucose infusion to evaluate glucose production and utilization. A control study with NaCl (154 mmol.l-1) infusion was also performed. The insulin levels during the clamps were similar in all studies (36 +/- 0.2 mU.l-1). Peak growth hormone levels were reached at 60 min (growth hormone 6 mU.kg-1.h-1: 31 +/- 5; growth hormone 12 mU.kg-1.h-1: 52 +/- 4 and growth hormone 24 mU.kg-1.h-1; 102 +/- 8 mU.l-1). The insulin-antagonistic effect of growth hormone started after approximately 2 h, was maximal after 4-5 h (approximately 39% inhibition of glucose infusion rate between control and growth hormone 24 mU.kg-1.h-1) and lasted for 6-7 h after peak levels. The resistance was due to a less pronounced insulin effect both to inhibit glucose production and to stimulate glucose utilization. Growth hormone infusion of 12 mU.kg-1.h-1 induced a similar insulin-antagonistic effect as the higher infusion rate whereas 6 mU.kg-1.h-1 induced a smaller response with a duration of 1 h between 3-4 h after peak levels of growth hormone. The present study demonstrates that growth hormone levels similar to those frequently seen in Type 1 (insulin-dependent) diabetic patients during poor metabolic control or hypoglycaemia, have pronounced insulin-antagonistic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The insulin-antagonistic effect of the counterregulatory hormones.

The counterregulatory hormones glucagon, adrenaline, cortisol and growth hormone are released during hypoglycaemia, and under other stress conditions. These hormones have insulin-antagonistic effects both in the liver and in the peripheral tissues. The insulin-antagonistic effects of glucagon and adrenaline are of rapid onset, whereas those of cortisol and growth hormone are only observed after a lag period of several hours. Glucagon is the most important hormone for acute glucose counterregulation. When the release of this hormone is deficient, as in patients with insulin-dependent diabetes, adrenaline becomes the most important hormone for glucose recovery during hypoglycaemia. Cortisol and growth hormone contribute to counterregulation during prolonged hypoglycaemia, but adrenaline is also of utmost importance in this condition. Adrenaline induces the early posthypoglycaemic insulin resistance, whereas cortisol and growth hormone are important for the insulin resistance that is observed later following hypoglycaemia. However, the importance of posthypoglycaemic insulin resistance for induction of posthypoglycaemic hyperglycaemia in clinical situations is limited. The pronounced insulin-antagonistic effect of growth hormone indicates that this hormone, in addition to its effect on the dawn phenomenon, could also play a key role in the regulation of other diurnal rhythms of glucose metabolism.

Animals↗
PubMed1990

Characterization of the late posthypoglycemic insulin resistance in insulin-dependent diabetes mellitus.

The insulin effect (6.5 to 7.5 hours) following hypoglycemia was studied with the euglycemic clamp technique in eight patients with insulin-dependent diabeteses mellitus (IDDM). The results were compared with a control study with the same insulin infusion, but where hypoglycemia was prevented by a glucose infusion. Glucose production (Ra) and utilization (Rd) were evaluated with D-(3-3H) glucose infusion. Hypoglycemia (glucose nadir, 1.5 +/- 0.1 mmol/L) caused a marked increase in cortisol and growth hormone, whereas the release of adrenaline and, in particular, glucagon was low. The plasma free insulin levels were similar in the studies, including during the clamp periods. The glucose infusion rates (GIR) were significantly lower after the hypoglycemia as compared with the control study (control, 2.4 +/- 0.3; hypoglycemia, 1.5 +/- 0.3 mg/kg x min; P less than .05). Thus, hypoglycemia induces prolonged insulin resistance. The posthypoglycemic insulin resistance during a moderate hyperinsulinemic (approximately 30 mU/L) clamp was mainly due to a decreased insulin effect on glucose utilization (control, 2.9 +/- 0.2; hypoglycemia, 2.2 +/- 0.2 mg/kg x min; P less than .02), whereas the insulin effect on glucose production was not significantly different after hypoglycemia.

Adult↗
PubMed1990

Postprandial hyperglycaemia following a morning hypoglycaemia in type 1 diabetes mellitus.

The occurrence of hyperglycaemia following a morning hypoglycaemic episode was studied in nine patients with Type 1 diabetes. Each patient was studied twice, once following induced hypoglycaemia and once in a control study when hypoglycaemia was prevented by glucose infusion. After the initial hypoglycaemic/control period the patients were maintained on their regular insulin regimens and were given standard meals. Hypoglycaemia induced postprandial hyperglycaemia (3.1 +/- 0.8 mmol l-1 above control) which lasted for about 8 h. Maximal growth hormone levels were seen 40 min after glucose nadir (control 7.8 +/- 3.2, hypoglycaemia 74.0 +/- 12.3 mU l-1) and the magnitude of the hyperglycaemia was related to the growth hormone levels following the hypoglycaemia (r = 0.80, p less than 0.01).

Adult↗
PubMed1989

Combined effect of growth hormone and cortisol on late posthypoglycemic insulin resistance in humans.

The occurrence and mechanisms for late (6.5- to 7.5-h) posthypoglycemic insulin resistance were studied with the euglycemic clamp in 19 healthy subjects. Comparisons were made with a control study with the same insulin infusion rate but where hypoglycemia was prevented by glucose infusion. Glucose production and utilization were studied with D-[3-3H] glucose infusions. Hypoglycemia induced marked insulin resistance shown by lower glucose infusion rates compared with the control study 3.1 +/- 0.3 vs. 6.0 +/- 0.7 mg.kg-1.min-1, P less than .001). This late posthypoglycemic insulin resistance was mainly due to a decreased insulin effect on glucose utilization. Infusion of propranolol did not prevent insulin resistance, whereas somatostatin partially prevented its appearance. Somatostatin plus metyrapone completely normalized posthypoglycemic insulin resistance. A positive correlation (r = .72, P less than .001) was found between initial insulin sensitivity and percent reduction of the insulin effect after hypoglycemia. Thus, hypoglycemia is followed by prolonged (6- to 8-h) insulin resistance. In contrast to early-phase (2- to 3-h) resistance, long-term resistance is not due to beta-adrenergic stimulation but to the combined effect of growth hormone and cortisol. This resistance is also more pronounced in subjects with initially high insulin sensitivity.

Adult↗