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Biomedical subjects

R A DeFronzo

Publications and source records attributed to R A DeFronzo.

At least 91 records · Page 5Linked to original sources
PubMed1993

Transmembrane glucose transport in skeletal muscle of patients with non-insulin-dependent diabetes.

Insulin resistance for glucose metabolism in skeletal muscle is a key feature in non-insulin-dependent diabetes mellitus (NIDDM). Which cellular effectors of glucose metabolism are involved is still unknown. We investigated whether transmembrane glucose transport in vivo is impaired in skeletal muscle in nonobese NIDDM patients. We performed euglycemic insulin clamp studies in combination with the forearm balance technique (brachial artery and deep forearm vein catheterization) in six nonobese NIDDM patients and five age- and weight-matched controls. Unlabeled D-mannitol (a nontransportable molecule) and radioactive 3-O-methyl-D-glucose (the reference molecular probe to assess glucose transport activity) were simultaneously injected into the brachial artery, and the washout curves were measured in the deep venous effluent blood. In vivo transmembrane transport of 3-O-methyl-D-glucose in forearm muscle was determined by computerized analysis of the washout curves. At similar steady-state plasma concentrations of insulin (approximately 500 pmol/liter) and glucose (approximately 5.15 mmol/liter), transmembrane inward transport of 3-O-methyl-D-glucose in skeletal muscle was markedly reduced in the NIDDM patients (6.5 x 10(-2) +/- 0.56 x 10(-2).min-1) compared with controls (12.5 x 10(-2) +/- 1.5 x 10(-2).min-1, P < 0.005). Mean glucose uptake was also reduced in the diabetics both at the whole body level (9.25 +/- 1.84 vs. 28.3 +/- 2.44 mumol/min per kg, P < 0.02) and in the forearm tissues (5.84 +/- 1.51 vs. 37.5 +/- 7.95 mumol/min per kg, P < 0.02). When the latter rates were extrapolated to the whole body level, skeletal muscle accounted for approximately 80% of the defect in insulin action seen in NIDDM patients. We conclude that transmembrane glucose transport, when assessed in vivo in skeletal muscle, is insensitive to insulin in nonobese NIDDM patients, and plays a major role in determining whole body insulin resistance.

Adult↗
PubMed1993

Glucose transport in human skeletal muscle. The in vivo response to insulin.

Transmembrane glucose transport plays a key role in determining insulin sensitivity. We have measured in vivo WBGU, FGU, and K(in) and K(out) of 3-O-methyl-D-glucose in forearm skeletal muscle by combining the euglycemic clamp technique, the forearm-balance technique, and a novel dual-tracer (1-[3H]-L-glucose and 3-O-[14C]-methyl-D-glucose) technique for measuring in vivo transmembrane transport. Twenty-seven healthy, lean subjects were studied. During saline infusion, insulin concentration, FGU (n = 6), K(in), and K(out) (n = 4) were similar to baseline. During SRIF-induced hypoinsulinemia (insulin < 15 pM, n = 4) WBGU was close to 0, and FGU, K(in), and K(out) were unchanged from basal (insulin = 48 pM) values. During insulin clamps at plasma insulin levels of approximately 180 (n = 4), approximately 420 (n = 5), approximately 3000 (n = 4), and approximately 9500 pM (n = 4), WBGU was 14.2 +/- 1.3, 34.2 +/- 4.1 (P < 0.05 vs. previous step), 55.8 +/- 1.8 (P < 0.05 vs. previous step), and 56.1 +/- 6.3 mumol.min-1.kg-1 of body weight (NS vs. previous step), respectively. Graded hyperinsulinemia concomitantly increased FGU from a basal value of 4.7 +/- 0.5 mumol.min-1.kg-1 up to 10.9 +/- 2.3 (P < 0.05 vs. basal value), 26.6 +/- 4.5 (P < 0.05 vs. previous step), 54.8 +/- 4.3 (P < 0.05 vs. previous step), and 61.1 +/- 10.8 mumol.min-1.kg-1 of forearm tissues (NS vs. previous step), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

In vivo glucose metabolism in obese and type II diabetic subjects with or without hypertension.

This study examined whether the presence of hypertension, an insulin-resistant condition, exacerbates the defect in insulin action observed in obesity and type II diabetes mellitus. Glucose metabolism in the basal state and in response to insulin was quantitated by using the euglycemic insulin (20 mU.min-1 x m-2) clamp in combination with 3-[3H]glucose infusion and indirect calorimetry in 20 obese nondiabetic subjects (10 hypertensive and 10 normotensive), 26 type II diabetic subjects (13 hypertensive and 13 normotensive), and 11 normal nondiabetic subjects. The two groups of obese subjects and the two groups of diabetic subjects were matched for sex, age, race, body mass index, and fat distribution. Both in the basal state and during insulin infusion, glucose disposal rates (total, oxidative, and nonoxidative) were similar in obese subjects with or without hypertension. Compared with control subjects, both groups of obese subjects were markedly insulin resistant. Similarly, type II diabetic individuals, whether normotensive or hypertensive, were equally insulin resistant. The severity of insulin resistance was nearly identical in obese and diabetic groups. In diabetic subjects, the inhibitory effect of insulin on hepatic glucose output, lipolysis, and lipid oxidation was blunted compared with normal subjects. In obese subjects the ability of insulin to inhibit lipolysis and lipid oxidation was impaired. However, hypertension did not alter the suppressive effects of insulin on hepatic glucose production, plasma free fatty acid levels, or lipid oxidation in either obese or type II diabetic subjects. These results indicate that hypertension does not confer a greater severity of insulin resistance than that already is present in obesity and type II diabetes mellitus.

Adipose Tissue↗
PubMed1993

Glucose metabolism during the menstrual cycle. Assessment with the euglycemic, hyperinsulinemic clamp.

To assess tissue sensitivity to insulin during the follicular and luteal phases of the menstrual cycle, two-step euglycemic, hyperinsulinemic clamp studies in combination with tritiated glucose infusion and indirect calorimetry were performed in regularly menstruating women in randomized order. There was no difference in the basal follicular and luteal phase levels of glucose, insulin or glucose turnover. A low-dose (0.25 mU/kg/min) insulin infusion suppressed endogenous hepatic glucose production. There was no difference in tissue insulin sensitivity during a high-dose insulin infusion (1.0 mU/kg/min). Nonoxidative glucose disposal also was similar in the basal and insulin infusion periods. Under euglycemic, hyperinsulinemic conditions, there is no difference in tissue sensitivity to insulin, and intracellular pathways of glucose disposal are not altered by the stage of the menstrual cycle.

Adult↗
PubMed1992

Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web.

Diabetes mellitus is commonly associated with systolic and diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive controls, a heightened plasma insulin response to a glucose challenge is found consistently. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. Using the insulin/glucose clamp technique in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth-muscle cells. Physiological maneuvers, such as caloric restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; good evidence indicates that these maneuvers also can lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia also are associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate density and low-density lipoproteins, both of which are atherogenic. Last, insulin per se, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth-muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth-muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of a variety of growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including type II diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.

Animals↗
PubMed1992

In vivo insulin action in genetic models of hypertension.

Insulin resistance has been described in nonobese subjects with essential hypertension. At present it is unknown whether hypertension per se may lead to the onset of insulin resistance. To examine this question we studied in vivo insulin action in two rat models of genetic hypertension. Four groups of conscious rats were studied: Milan hypertensive (MHS), Milan normotensive (MNS), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY). Mean arterial pressure was increased in SHR vs. WKY in both the fed (184 +/- 5 vs. 126 +/- 6 mmHg; P less than 0.001) and fasting (160 +/- 5 vs. 129 +/- 5; P less than 0.001) states. During high-dose insulin clamps, total body glucose uptake (mg.kg-1.min-1) was similar in MNS (28.7 +/- 1.4) vs. MHS (33.6 +/- 3.0) and in WKY (34.6 +/- 1.8) vs. SHR (35.7 +/- 2.4). During low-dose insulin clamps, suppression of hepatic glucose production (3.5 +/- 0.6 vs. 3.0 +/- 0.5 mg.kg-1.min-1) and stimulation of glycolysis (12.9 +/- 0.8 vs. 14.4 +/- 1.5 mg.kg-1.min-1) were similar in WKY vs. SHR, whereas glucose uptake (24.6 +/- 1.9 vs. 18.3 +/- 1.2 mg.kg-1.min-1; P less than 0.01) and muscle glycogenic rate (10.2 +/- 1.1 vs. 6.5 +/- 1.1 mg.kg-1.min-1; P less than 0.05) were increased in SHR vs. WKY. In conclusion, 1) feeding markedly augments blood pressure in hypertensive but not in normotensive rats, and 2) hepatic and muscle insulin sensitivity are normal or increased in two different rat models of genetic hypertension. These results provide evidence that high blood pressure per se does not invariably lead to the development of insulin resistance.

Animals↗
PubMed1992

Effect of insulin on oxidative and nonoxidative pathways of free fatty acid metabolism in human obesity.

The dose-response relationship between the plasma insulin concentration and oxidative and nonoxidative pathways of free fatty acid (FFA) metabolism was examined in 11 obese and 7 lean subjects using a stepwise insulin clamp technique in combination with indirect calorimetry and infusion of [1-14C]palmitate. The fasting plasma FFA concentration was elevated in obese subjects (793 +/- 43 vs. 642 +/- 39 mumol/l; P less than 0.01) and was associated with an increased basal rate of plasma FFA turnover, FFA oxidation, and nonoxidative FFA disposal, i.e., reesterification (all P less than 0.01). Suppression of plasma FFA turnover by physiological increments in plasma insulin was impaired in obese compared with lean subjects. However, plasma FFA turnover expressed per kilogram fat mass was normally suppressed by insulin in obese subjects. Although insulin suppressed plasma FFA oxidation to the same extent in lean and obese subjects, inhibition of total lipid oxidation by insulin was impaired in the obese group. Obese subjects had an enhanced basal rate of nonoxidative FFA disposal, which was suppressed less by physiological increments in plasma insulin compared with lean controls. Therefore, we conclude that 1) lipolysis in uncomplicated obesity is normally sensitive to insulin; the enhanced FFA flux is simply a consequence of the increased fat mass. 2) Nonoxidative FFA disposal expressed per lean body mass is enhanced in obese subjects and correlates with the increase in plasma FFA concentration and fat mass. 3) Enhanced oxidation of intracellular lipids contributes to the enhanced rate of total lipid oxidation in obese subjects.

Fatty Acids, Nonesterified↗
PubMed1992

Glucose and amino acid metabolism in chronic renal failure: effect of insulin and amino acids.

The effects of hyperinsulinemia and hyperaminoacidemia on glucose and amino acid metabolism were examined in 16 control and 13 chronic renal failure (CRF) patients under two conditions: 1) euglycemic hyperinsulinemia and 2) amino acid infusion. All studies were performed with continuous indirect calorimetry and [1-14C]leucine infusion. In CRF patients insulin-mediated whole body glucose metabolism was reduced by 35% (4.41 +/- 0.50 vs. 6.76 +/- 0.73 mg.kg-1.min-1, P less than 0.01), primarily due to a decrease in nonoxidative glucose disposal (1.70 +/- 0.70 vs. 4.32 +/- 0.60 mg.kg-1.min-1, P less than 0.01); glucose oxidation was similar in both groups. In the postabsorptive state total leucine turnover (1.56 +/- 0.06 vs. 1.75 +/- 0.06), leucine oxidation (0.25 +/- 0.01 vs. 0.30 +/- 0.01), and nonoxidative leucine disposal (1.29 +/- 0.06 vs. 1.40 +/- 0.07 mumol.kg-1.min-1) were reduced in CRF vs. control subjects (all P less than 0.05). In response to hyperinsulinemia, endogenous leucine flux (index of proteolysis), leucine oxidation, nonoxidative leucine disposal (NOLD) (index of protein synthesis), and net leucine flux into protein were similar in CRF and control subjects. In contrast, the ability of hyperaminoacidemia to enhance NOLD (1.54 +/- 0.11 vs. 2.10 +/- 0.10 mumol.kg-1.min-1, P less than 0.01) and net leucine balance (0.27 +/- 0.05 vs. 0.41 +/- 0.05, P less than 0.05) was reduced in CRF patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents.

NIDDM patients with overt fasting hyperglycemia are characterized by multiple defects involving both insulin secretion and insulin action. At this point of the natural history of NIDDM, however, it is difficult to establish which defects are primary and which are acquired secondary to insulinopenia and chronic hyperglycemia. To address this question, we have studied the glucose-tolerant offspring (probands) of two Mexican-American NIDDM parents. Such individuals are at high risk for developing NIDDM later in life. The probands are characterized by hyperinsulinemia in the fasting state and in response to both oral and intravenous glucose. Insulin-mediated glucose disposal (insulin clamp technique), measured at two physiological levels of hyperinsulinemia (approximately 240 and 450 pM [approximately 40 and 75 microU/ml]), was reduced by 43 and 33%, respectively. During both the low- and high-dose insulin clamp steps, impaired nonoxidative glucose disposal, which primarily represents glycogen synthesis, was the major defect responsible for the insulin resistance. During the lower dose insulin clamp step only, a small decrease in glucose oxidation was observed. No defect in suppression of HGP by insulin was demonstrable. The ability of insulin to inhibit lipid oxidation (measured by indirect calorimetry) and plasma FFA concentration was impaired at both levels of hyperinsulinemia. These results indicate that the glucose-tolerant offspring of two NIDDM parents are characterized by hyperinsulinemia and manifest all of the metabolic abnormalities that characterize the fully established diabetic state, including insulin resistance, a major impairment in nonoxidative glucose disposal, a quantitatively less important defect in glucose oxidation, and a diminished insulin-mediated suppression of lipid oxidation and plasma FFA concentration.

Adult↗
PubMed1992

Pathogenesis of NIDDM. A balanced overview.

Non-insulin-dependent diabetes mellitus (NIDDM) results from an imbalance between insulin sensitivity and insulin secretion. Both longitudinal and cross-sectional studies have demonstrated that the earliest detectable abnormality in NIDDM is an impairment in the body's ability to respond to insulin. Because the pancreas is able to appropriately augment its secretion of insulin to offset the insulin resistance, glucose tolerance remains normal. With time, however, the beta-cell fails to maintain its high rate of insulin secretion and the relative insulinopenia (i.e., relative to the degree of insulin resistance) leads to the development of impaired glucose tolerance and eventually overt diabetes mellitus. The cause of pancreatic "exhaustion" remains unknown but may be related to the effect of glucose toxicity in a genetically predisposed beta-cell. Information concerning the loss of first-phase insulin secretion, altered pulsatility of insulin release, and enhanced proinsulin-insulin secretory ratio is discussed as it pertains to altered beta-cell function in NIDDM. Insulin resistance in NIDDM involves both hepatic and peripheral, muscle, tissues. In the postabsorptive state hepatic glucose output is normal or increased, despite the presence of fasting hyperinsulinemia, whereas the efficiency of tissue glucose uptake is reduced. In response to both endogenously secreted or exogenously administered insulin, hepatic glucose production fails to suppress normally and muscle glucose uptake is diminished. The accelerated rate of hepatic glucose output is due entirely to augmented gluconeogenesis. In muscle many cellular defects in insulin action have been described including impaired insulin-receptor tyrosine kinase activity, diminished glucose transport, and reduced glycogen synthase and pyruvate dehydrogenase. The abnormalities account for disturbances in the two major intracellular pathways of glucose disposal, glycogen synthesis, and glucose oxidation. In the earliest stages of NIDDM, the major defect involves the inability of insulin to promote glucose uptake and storage as glycogen. Other potential mechanisms that have been put forward to explain the insulin resistance, include increased lipid oxidation, altered skeletal muscle capillary density/fiber type/blood flow, impaired insulin transport across the vascular endothelium, increased amylin, calcitonin gene-related peptide levels, and glucose toxicity.

Diabetes Mellitus, Type 2↗
PubMed1991

Effect of strict glycemic control on renal hemodynamic response to amino acids and renal enlargement in insulin-dependent diabetes mellitus.

BACKGROUND: Many patients with insulin-dependent diabetes mellitus have an increase in the glomerular filtration rate and renal enlargement early in the course of their disease. Both these changes may be risk factors for the later development of diabetic nephropathy. Their cause is not known, but they could be due to augmented renal responses to the increase in plasma amino acid concentrations that occurs when dietary protein intake is high, a factor known to increase glomerular filtration and renal blood flow in normal subjects. METHODS: We measured the glomerular filtration rate and renal plasma flow after an overnight fast and during an infusion of amino acids in 12 patients with insulin-dependent diabetes mellitus and 9 normal subjects. The diabetic patients were studied when they were hyperglycemic, when they were euglycemic after an insulin infusion for 36 hours, and after intensive insulin therapy for 3 weeks. Kidney volume was measured by ultrasonography before and after the period of intensive insulin therapy. RESULTS: The glomerular filtration rate and renal plasma flow were normal after fasting when the patients were hyperglycemic (mean [+/- SE] fasting plasma glucose level, 11.5 +/- 0.7 mmol per liter). After the amino acid infusion, these values increased more in the patients (glomerular filtration rate, 2.65 +/- 0.07 ml per second per 1.73 m2 of body-surface area; renal plasma flow, 13.30 +/- 0.68 ml per second per 1.73 m2; P less than 0.05 for both) than in the normal subjects (2.25 +/- 0.08 and 11.20 +/- 0.65 ml per second per 1.73 m2, respectively). The 36-hour infusion of insulin in the diabetic patients did not alter the glomerular filtration rate or renal plasma flow either before or during the amino acid infusion. After three weeks of intensive insulin therapy (fasting plasma glucose level, 5.3 +/- 0.2 mmol per liter), the glomerular filtration rate and renal plasma flow after the amino acid infusion (2.33 +/- 0.03 and 11.30 +/- 0.43 ml per second per 1.73 m2, respectively) were similar to those in the normal subjects. The kidney volumes in the normal subjects and the patients with diabetes were 219 +/- 14 and 312 +/- 14 ml per 1.73 m2, respectively (P less than 0.01); the volume decreased to 267 +/- 22 ml per 1.73 m2 (P less than 0.001) in the diabetic patients after three weeks of intensive insulin therapy, which was not significantly different from the volume in the normal subjects (P = 0.1). CONCLUSIONS: Conventionally treated diabetic patients who have normal renal function while fasting have augmented renal hemodynamic responses to increased plasma amino acid concentrations. The concomitant decrease in these hemodynamic responses and in kidney size with strict glycemic control suggests that these phenomena are related and influenced by the metabolic state.

Adult↗
PubMed1991

Effect of sulphonylurea on glucose-stimulated insulin secretion in healthy and non-insulin dependent diabetic subjects: a dose-response study.

The effect of a rapid-acting sulphonylurea, glipizide, on the dose-response relationship between the beta-cell response (insulin and C-peptide secretion) and the ambient plasma glucose concentration was examined in 12 healthy and 6 non-insulin-dependent diabetic subjects. The subjects participated in two sets of experiments which were performed in random order: (A) four hyperglycaemic clamp studies, during which the plasma glucose concentration was raised for 120 min by 1 (only in healthy subjects), 3, 7, and 17 mmol/l; and (B) the same four hyperglycaemic clamp studies preceded by ingestion of 5 mg glipizide. All subjects participated in a further study, in which glipizide was ingested and the plasma glucose concentration was maintained at the basal level. In control subjects in the absence of glipizide, the first-phase plasma insulin response (0-10 min) increased progressively with increasing plasma glucose concentration up to 10 mmol/l, above which it tended to plateau. Glipizide augmented the first-phase insulin response without changing the slope of the regression line relating plasma insulin to glucose concentrations. The second-phase plasma insulin response (20-120 min) increased linearly with increasing hyperglycaemia (r = 0.997). Glipizide alone increased the plasma insulin response by 180 pmol/l. A similar increase in plasma insulin response following glipizide was observed at each hyperglycaemic step, indicating that glipizide did not affect the sensitivity of the beta-cell to glucose. First-phase insulin secretion was reduced in the type 2 (non-insulin-dependent) diabetic patients, and was not influenced by glipizide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Insulin resistance in noncirrhotic idiopathic portal hypertension.

To explore further the pathogenesis of glucose intolerance and insulin resistance observed in patients with cirrhosis and portal hypertension, we studied a 35-year-old woman with presinusoidal portal hypertension without cirrhosis due to nodular regenerative hyperplasia of the liver. After oral glucose ingestion, glucose tolerance remained normal; however, this occurred at the expense of a markedly hyperinsulinemic plasma response, suggesting the presence of insulin resistance. To examine this question more directly, we performed a stepwise euglycemic insulin clamp study in combination with an infusion of [6-3H]glucose and [1-14C]palmitate and indirect calorimetry. The ability of insulin to promote total body (primarily muscle) glucose uptake was markedly impaired, whereas its effect to suppress hepatic glucose production was normal compared with results obtained in nine healthy subjects. Moreover, insulin failed to normally suppress plasma free fatty acid turnover and oxidation in this patient. This informative case demonstrates that portal hypertension alone, without hepatic dysfunction from cirrhosis, is associated with impaired insulin-mediated glucose and plasma free fatty acid metabolism and may also play a predominant role in the development of insulin resistance in many cirrhotic patients.

Adult↗
PubMed1991

Differential effect of hyperglycemia and hyperinsulinemia on pathways of hepatic glycogen repletion.

To delineate the roles of hyperglycemia and insulin on the direct vs. indirect pathways of liver glycogen synthesis, we performed euglycemic (group I; n = 8), hyperglycemic (group II; n = 9), and euglycemic pharmacological hyperinsulinemic clamp studies (120 min) with an infusion of [1-13C]glucose in chronically catheterized conscious rats after a 24-h fast. Portal vein plasma glucose concentrations and portal vein plasma insulin concentrations, respectively, obtained at the end of the study in groups I-III were as follows: group I 110 +/- 4 mg/dl, 29 +/- 7 ng/ml; group II 219 +/- 7 mg/dl, 24 +/- 7 ng/ml; and group III 112 +/- 9 mg/dl, 174 +/- 25 ng/ml. Mean liver glycogen concentrations at the end of the three studies were 0.68 +/- 0.07, 1.22 +/- 0.08 (P less than 0.001 compared with groups I and III), and 0.60 +/- 0.17 g/100 g wet wt liver in groups I-III respectively, which yielded hepatic glycogen synthetic rates of 0.16 +/- 0.03, 0.41 +/- 0.04 (P less than 0.001 compared with groups I and III), and 0.13 +/- 0.08 mumol glucosyl U.g liver-1.min-1 in groups I-III, respectively. From the enrichments of 13C in the C-1 and C-6 positions of the glucosyl unit in glycogen compared with the enrichment in the C-1 position in portal vein glucose as determined by 13C- and 1H-NMR, the amount of glycogen synthesized by the direct pathway was calculated to be 18 +/- 2, 41 +/- 3 (P less than 0.0001 compared with groups I and III), and 17 +/- 3% in groups I-III, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Role of free fatty acids and insulin in determining free fatty acid and lipid oxidation in man.

Plasma FFA oxidation (measured by infusion of 14C-palmitate) and net lipid oxidation (indirect calorimetry) are both inhibited by insulin. The present study was designed to examine whether these insulin-mediated effects on lipid metabolism resulted from a decline in circulating FFA levels or from a direct action of the hormone on FFA/lipid oxidation. Nine subjects participated in two euglycemic insulin clamps, performed with and without heparin. During each insulin clamp study insulin was infused at two rates, 4 and 20 mU/m2.min for 120 min. The studies were performed with indirect calorimetry and 3-3H-glucose and 14C-palmitate infusion. During the control study plasma FFA fell from 610 +/- 46 to 232 +/- 42 to 154 +/- 27 mumol/liter, respectively. When heparin was infused basal plasma FFA concentration remained constant. During the control study, FFA/lipid oxidation rates decreased in parallel with the fall in the plasma FFA concentration. During the insulin/heparin study, plasma 14C-FFA oxidation remained unchanged while net lipid oxidation decreased. In conclusion, when the plasma FFA concentration is maintained unchanged by heparin infusion, insulin has no direct effect on FFA turnover and disposal. These results thus suggest that plasma FFA oxidation is primarily determined by the plasma FFA concentration, while net lipid oxidation is regulated by both the plasma FFA and the insulin level.

Adult↗