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Biomedical subjects

V A Koivisto

Publications and source records attributed to V A Koivisto.

At least 91 records · Page 5Linked to original sources
PubMed1992

Defect in insulin action on expression of the muscle/adipose tissue glucose transporter gene in skeletal muscle of type 1 diabetic patients.

Recently several members of the glucose transporter family have been identified by molecular cloning techniques. We determined the effect of a 4-h insulin infusion on the expression of the muscle/adipose tissue (GLUT-4) glucose transporter mRNA and protein in 14 insulin-treated type 1 diabetic patients and 15 matched nondiabetic subjects. GLUT-4 mRNA and protein concentrations were determined in muscle biopsies taken before and at the end of the insulin infusion during maintenance of normoglycemia. In response to insulin, muscle GLUT-4 mRNA increased in the nondiabetic subjects from 24 +/- 3 to 36 +/- 4 pg/microgram RNA (P less than 0.001) but remained unchanged in the insulin-resistant diabetic patients (24 +/- 2 vs. 26 +/- 2 pg/microgram RNA, before vs. after insulin). The glucose transporter protein concentrations were similar in the basal state and decreased by 21 +/- 7% (P less than 0.02) in the normal subjects but remained unchanged in the diabetic patients. The increase of the GLUT-4 mRNA and the decrease in the GLUT-4 protein correlated with the rate of glucose uptake [correlation coefficient (r) = -0.55, P less than 0.01, and r = -0.44, P less than 0.05, respectively]. We conclude that the insulin response of both the GLUT-4 glucose transporter mRNA and protein are absent in skeletal muscle of insulin-resistant type 1 diabetic patients. Thus, impaired insulin regulation of glucose transporter gene expression can be one of the underlying mechanisms of insulin resistance in type 1 diabetes.

Adipose Tissue↗
PubMed1992

Growth hormone and insulin-like growth factor regulate insulin-like growth factor-binding protein-1 in Laron type dwarfism, growth hormone deficiency and constitutional short stature.

Insulin-like growth factors (IGFs) mediate the effects of growth hormone (GH), and the insulin-like growth factor-binding proteins (IGFBPs) modulate the actions of IGFs in tissues. We studied the circulating levels of IGFBP-1 in 6 children and 9 adults with Laron type dwarfism (LTD), in 11 children and 21 adults with growth hormone deficiency (GHD), and in 8 children with constitutional short stature. Compared with the situation in healthy children, the basal serum IGFBP-1 concentration was 5.4-fold higher in LTD children, 4.1-fold higher in GHD children, and 3.8-fold higher in children with short stature (p < 0.02 vs controls in all groups). In adult patients with multiple pituitary hormone deficiency (MPHD), the IGFBP-1 concentration was 2-fold elevated, but it was normal in adult LTD patients. Intravenous (N = 10) or subcutaneous (N = 9) administration of IGF-I (75 micrograms.kg-1 and 150 micrograms.kg-1, respectively) in LTD children resulted in a rapid 50-60% fall in serum insulin (p < 0.02), a decline in blood glucose and a concomitant 40-60% rise of IGFBP-1 levels (p < 0.05). Treatment for seven days with IGF-I (150 micrograms.kg-1 x d-1) resulted in a decrease by 34% and 44% of serum IGFBP-1 level in two out of three children with LTD. After prolonged GH therapy, the IGFBP-1 level fell in GHD children by 29% (p < 0.05), in GHD adults by 52% (p < 0.02) and in children with constitutional short stature by 17% (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Mechanisms of hyperglycemia-induced insulin resistance in whole body and skeletal muscle of type I diabetic patients.

To examine the mechanisms of hyperglycemia-induced insulin resistance, eight insulin-dependent (type I) diabetic men were studied twice, after 24 h of hyperglycemia (mean blood glucose 20.0 +/- 0.3 mM, i.v. glucose) and after 24 h of normoglycemia (7.1 +/- 0.4 mM, saline) while receiving identical diets and insulin doses. Whole-body and forearm glucose uptake were determined during a 300-min insulin infusion (serum free insulin 359 +/- 22 and 373 +/- 29 pM, after hyper- and normoglycemia, respectively). Muscle biopsies were taken before and at the end of the 300-min insulin infusion. Plasma glucose levels were maintained constant during the 300-min period by keeping glucose for 150 min at 16.7 +/- 0.1 mM after 24-h hyperglycemia and increasing it to 16.5 +/- 0.1 mM after normoglycemia and by allowing it thereafter to decrease in both studies to normoglycemia. During the normoglycemic period (240-300 min), total glucose uptake (25.0 +/- 2.8 vs. 33.8 +/- 3.9 mumol.kg-1 body wt.min-1, P less than 0.05) was 26% lower, forearm glucose uptake (11 +/- 4 vs. 18 +/- 3 mumol.kg-1 forearm.min-1, P less than 0.05) was 35% lower, and nonoxidative glucose disposal (8.9 +/- 2.2 vs. 19.4 +/- 3.3 mumol.kg-1 body wt-1min-1, P less than 0.01) was 54% lower after 24 h of hyper- and normoglycemia, respectively. Glucose oxidation rates were similar. Basal muscle glycogen content was similar after 24 h of hyperglycemia (234 +/- 23 mmol/kg dry muscle) and normoglycemia (238 +/- 22 mmol/kg dry muscle). Insulin increased muscle glycogen to 273 +/- 22 mmol/kg dry muscle after 24 h of hyperglycemia and to 296 +/- 33 mmol/kg dry muscle after normoglycemia (P less than 0.05 vs. 0 min for both). Muscle ATP, free glucose, glucose-6-phosphate, and fructose-6-phosphate concentrations were similar after both 24-h treatment periods and did not change in response to insulin. We conclude that a marked decrease in whole-body, muscle, and nonoxidative glucose disposal can be induced by hyperglycemia alone.

Adenosine Triphosphate↗
PubMed1992

Fuel and fluid homeostasis during long-term exercise in healthy subjects and type I diabetic patients.

OBJECTIVE: This study was designed to examine metabolic and hormonal effects of long-term exercise in healthy subjects and insulin-dependent (type I) diabetic patients. RESEARCH DESIGN AND METHODS: Two studies were performed. First, 16 healthy males (32 +/- 3 yr) were studied during a semitriathlon competition (2 km swimming, 90 km biking, and 21 km running). Second, 9 type I diabetic males (41 +/- 2 yr) and 17 healthy matched control subjects were studied during a 75 km cross-country skiing race. Blood samples were taken before and immediately after exercise, and also during the ski race. RESULTS: During the semitriathlon race, serum insulin, C-peptide, glucagon cortisol, growth hormone ACTH, prolactin, and plasma renin activity increased two- to ninefold, whereas serum testosterone fell. Apart from a fall in magnesium, serum electrolyte concentrations remained unchanged. Before long-term skiing, patients reduced their insulin dose by 30-40%. They were hyperglycemic during the initial part of the race, but near normoglycemic thereafter. There were large interindividual variations in the increments of counterregulatory hormones, whereas serum testosterone and luteinizing hormone fell quite uniformly. Plasma renin activity and aldosterone concentrations rose similarly in diabetic and healthy subjects, whereas the rise in antidiuretic hormone was slightly greater in diabetic patients. During the initial part of the race, serum atrial natriuretic peptide fell in both groups. CONCLUSIONS: Severalfold increments in hormone concentrations contribute to the maintenance of fuel and fluid homeostasis during long-term exercise. With an appropriate adjustment of insulin dose and diet, also type I diabetic patients can participate in competitive long-term exercise.

Adult↗
PubMed1991

Level of skeletal muscle glucose transporter protein correlates with insulin-stimulated whole body glucose disposal in man.

The content of GLUT4 glucose transporter mRNA and protein were measured in samples of the vastus lateralis muscle of normal volunteers subjected to a 4-h hyperinsulinaemic, euglycaemic clamp. Plasma glucose concentration was clamped at 5.3 +/- 0.1 mmol/l, and serum insulin concentration was maintained at 740 +/- 5 pmol/l. Whole body glucose uptake averaged 38.3 +/- 2.2 mumol.kg-1.min-1, 62% of this being due to disposal via non-oxidative pathways. A significant correlation existed between basal levels of GLUT4 protein and the rate of whole body glucose disposal (r = 0.77, p less than 0.02) and non-oxidative glucose disposal (r = 0.80, p less than 0.02). There was no correlation between GLUT4 protein content and oxidative glucose disposal (r = 0.08, NS). These observations are consistent with an important role for skeletal muscle GLUT4 protein in whole body glucose disposal.

Adult↗
PubMed1991

Follow-up of cyclosporin A treatment in type 1 (insulin-dependent) diabetes mellitus: lack of long-term effects.

In the Canadian/European randomized controlled study on cyclosporin A (CsA) in recent onset Type 1 (insulin-dependent) diabetes, treatment with the immunosuppressive drug had increased and maintained Beta-cell function and clinical remission during the first 12 months. Following discontinuation of the study drug and double-blinding after a mean of 13.8 months former CsA patients doubled the daily insulin dose within 6 months reaching the level of former placebo patients. The difference in Beta-cell function between the two groups was also lost. Metabolic control (HbA1c) was transiently worse in the former CsA group. Adverse effects of cyclosporin A on systolic blood pressure, haemoglobin levels, serum potassium and creatinine levels also remitted during that time. We conclude that treatment with cyclosporin A for a mean of 13.8 months had no long-lasting effect on the course of Type 1 diabetes persisting beyond drug discontinuation.

Adolescent↗
PubMed1991

Hormone response of diabetic patients to exercise at cool and warm temperatures.

Both exercise and high ambient temperatures stimulate the secretion of counterregulatory hormones which can change glucose homeostasis. We studied whether in diabetic patients there are any differences in the hormonal response to exercise performed at cool or warm ambient temperatures. A study was performed on eight male insulin-dependent patients at rest and during exercise at +10 degrees C and +30 degrees C. Exercise consisted of three consecutive 15-min periods at 60% of maximal aerobic capacity. The concentrations of plasma lactate and counterregulatory hormones at rest were similar at warm and cool temperature, whereas prolactin concentration was higher (P less than 0.01) at +30 degrees C. Exercise resulted in an increase in noradrenaline, growth hormone and prolactin (P less than 0.01), prevented the diurnal decrease in cortisol, but had no effect on glucagon. Hormone responses to exercise were similar at +10 degrees C and at +30 degrees C, except for cortisol and noradrenaline which showed greater responses at warm than at cool temperatures. This may have been due to the higher relative work load at warm compared to cool temperatures as suggested by the higher heart rate and greater increase of lactate at +30 degrees C. These data indicate that within a range of ambient temperatures commonly occurring in sports, the response of counterregulatory hormones is largely independent of ambient temperature in insulin-dependent diabetic patients.

Adult↗
PubMed1991

Effect of free fatty acids on glucose uptake and nonoxidative glycolysis across human forearm tissues in the basal state and during insulin stimulation.

We tested whether FFAs influence glucose uptake by human peripheral tissues in vivo. Whole body glucose uptake, FFA turnover, energy expenditure and substrate oxidation rates, forearm glucose and FFA uptake, and nonoxidative glycolysis (net release of alanine and lactate) were measured in 14 normal male subjects in the basal state (0-240 min; serum insulin, approximately 5 microU/mL) and during euglycemic hyperinsulinemia (240-360 min; approximately 75 microU/mL) on 2 separate occasions, once during elevation of plasma FFA by infusions of Intralipid and heparin (plasma FFA, 4.6 +/- 0.1 vs. 4.2 +/- 0.4 mmol/L; 180-240 vs. 300-360 min) and once during infusion of saline (plasma FFA, 0.50 +/- 0.07 vs. 0.02 +/- 0.07 mmol/L, respectively). In the basal state, whole body glucose disposal remained unchanged, but the fate of glucose was significantly altered toward diminished oxidation (7.3 +/- 0.8 vs. 5.6 +/- 0.5 mumol/kg.min; P less than 0.05, saline vs. Intralipid) and increased nonoxidative glycolysis (P less than 0.05). Elevation of plasma FFA significantly increased forearm glucose uptake (1.0 +/- 0.6 vs. 2.4 +/- 0.7 mumol/kg.min; P less than 0.01) and nonoxidative glycolysis (net release of alanine and lactate, 0.4 +/- 0.5 vs. 1.2 +/- 0.4 mumol glucose equivalents/kg.min; P less than 0.05). During hyperinsulinemia, FFA decreased whole body glucose disposal (38 +/- 2 vs. 30 +/- 3 mumol/kg.min; P less than 0.001) due to a decrease in glucose oxidation (13 +/- 1 vs. 7 +/- 1 mumol/kg.min; P less than 0.01, saline vs. Intralipid), and forearm glucose uptake (31 +/- 4 vs. 24 +/- 6 mumol/kg.min; P less than 0.01, saline vs. Intralipid). Under these conditions, 7 +/- 2% and 3 +/- 1% (P less than 0.05) of forearm glucose uptake could be accounted for by nonoxidative glycolysis in the Intralipid and saline studies, respectively. In summary, 1) elevation of plasma FFA concentrations suppresses the rate of carbohydrate oxidation to a rate that, both basally and during hyperinsulinemia, is similar to that reported for insulin-independent glucose oxidation in the brain; 2) basally, forearm glucose uptake is increased by FFA; and 3) during hyperinsulinemia, FFA inhibit glucose uptake by forearm tissues. We conclude that the interaction between glucose and FFA fuels in human forearm tissues is dependent upon the ambient insulin concentration; the increase in basal glucose uptake would be compatible with the increase need of glucose for FFA reesterification; the decrease in insulin-stimulated glucose uptake supports operation of the glucose-FFA cycle in human forearm tissues.

Adult↗
PubMed1991

No reduction in total hepatic glucose output by inhibition of gluconeogenesis with ethanol in NIDDM patients.

Increased gluconeogenesis has been suggested to account for all of the increase in basal glucose production in patients with non-insulin-dependent diabetes mellitus (NIDDM). We studied the effect of inhibition of gluconeogenesis with ethanol on total hepatic glucose output (HGO) in patients with NIDDM. Fourteen patients with NIDDM (mean +/- SE age 61 +/- 2 yr, fasting plasma glucose 11.4 +/- 0.8 mM; body mass index 27 +/- 1 kg/m2) were studied twice after an overnight fast, once during ethanol administration (blood ethanol approximately 12 mM) and once during saline administration. Total HGO rate was measured with [3H]glucose. Inhibition of gluconeogenesis by ethanol was followed qualitatively with [U-14C]lactate (n = 8) and [U-14C]glycerol (n = 6) as tracers. Ethanol inhibited gluconeogenesis from lactate by 71 +/- 5% (0.5 +/- 0.2 vs. 1.8 +/- 0.1 mumol glucose.kg-1.min-1, 240-300 min, P less than 0.001; ethanol vs. saline, P less than 0.001) and from glycerol by 65 +/- 6% (0.8 +/- 0.2 vs. 2.3 +/- 0.6 mumol glucose.kg.min-1, P less than 0.001). Total HGO rate remained unchanged and averaged 12.8 +/- 1.8 and 11.8 +/- 2.1 mumol.kg-1.min-1 in the saline and ethanol studies, respectively (NS). We concluded that inhibition of gluconeogenesis by ethanol does not decrease total HGO in patients with NIDDM. Our results suggest the existence of a regulatory mechanism in the liver that maintains constant total HGO despite inhibition of gluconeogenesis.

Aged↗
PubMed1990

No evidence for isotope discrimination of tritiated glucose tracers in measurements of glucose turnover rates in man.

Under non-steady-state conditions, glucose turnover rates determined with tritiated glucose tracers are often underestimated. To examine whether isotope discrimination or a tracer contaminant can contribute to this, we compared the turnover rates of unlabelled and tritiated glucose under isotopic steady-state conditions. The turnover rates were measured in 20 healthy subjects at two insulin concentrations (79 +/- 3 mU.l-1 and 704 +/- 62 mU.l-1). Euglycaemia was maintained by infusing unlabelled glucose mixed with (3(3)H)- or (6(3)H)-glucose. In both studies, the isotopically determined glucose disposal rate was virtually identical to the exogenous glucose infusion rate (low insulin 7.66 +/- 0.48 vs 7.58 +/- 0.44 mg.kg-1.min-1, high insulin 13.36 +/- 0.74 vs 13.55 +/- 0.98 mg.kg-1.min-1). The individual values were correlated in both the low (r = 0.85, p less than 0.001) and high dose insulin (r = 0.81, p less than 0.001) studies. Tritiated glucose specific activities were also compared in arterialized and deep venous blood across forearm tissues during the high-dose insulin infusion. Glucose specific activities were similar in arterialized and deep venous blood when analysed with HPLC and conventional methods. In summary: (1) Under isotopic steady-state conditions the turnover rates of unlabelled and labelled glucoses are similar. (2) Unlabelled and labelled glucose are handled identically across forearm tissues. (3) We found no tracer impurity in our tritiated glucose preparations. We conclude that (3(3)H)- and (6(3)H)-glucose tracers can be used to reliably measure glucose turnover rates in man.

Adult↗
PubMed1990

Localization of rate-limiting defect for glucose disposal in skeletal muscle of insulin-resistant type I diabetic patients.

We searched for metabolic crossover points in muscle glucose metabolite profiles during maintenance of matched glucose fluxes across forearm muscle in insulin-resistant type I (insulin-dependent) diabetic patients and nondiabetic subjects. To classify subjects as insulin sensitive or insulin resistant, whole-body and forearm glucose disposal, oxidative and nonoxidative glucose disposal (indirect calorimetry), and glycogen synthesis (muscle glycogen content in needle biopsies) were measured under euglycemic conditions at two insulin concentrations. Whole-body and forearm muscle glucose disposal were significantly reduced in diabetic patients compared with control subjects. The reduction in total glucose disposal was due to similar relative reductions in oxidative and nonoxidative glucose disposal, pointing toward rate limitation early in glucose metabolism. The defect in nonoxidative glucose disposal was at least partly due to a defect in muscle glycogen synthesis, because muscle glycogen content failed to increase in response to an increase in the plasma insulin concentration in the diabetic patients. The most-insulin-resistant type 1 diabetic patients were restudied under conditions where, by glucose mass action, whole-body glucose disposal was forced to be similar to that in the control subjects. Matching glucose fluxes in the two groups resulted in similar rates of forearm and whole-body oxidative and nonoxidative glucose disposal and muscle glycogen synthesis, but it did not result in accumulation of free intracellular glucose, glucose-6-phosphate, glucose-1-phosphate, fructose-6-phosphate, or lactate in muscle. These data imply that the rate-limiting defect for glucose disposal in skeletal muscle of type I diabetic patients is at the level of glucose transport.

Adult↗
PubMed1990

Changes in muscle glucose metabolism in type 1 diabetes.

Patients with type 1 diabetes are characterized by an average 40% reduction in the insulin sensitivity. In newly diagnosed patients, insulin resistance is due to insulin deficiency and its metabolic consequences. After the beginning of insulin therapy, insulin sensitivity transiently improves, but deteriorates again after 6-9 months of insulin therapy. Insulin resistance is mainly due to a reduction in glucose uptake by muscle tissue. There are similar relative reductions in both oxidative and nonoxidative glucose disposal. When glucose disposal is determined under similar plasma glucose and insulin concentrations, glucose oxidation, the activity of pyruvate dehydrogenase and glycogen synthase are all reduced. If glucose disposal rate in diabetic patients is normalized by glucose mass action, both oxidative and nonoxidative glucose disposal and glycogen synthase activity become normal. As the normalization of glucose disposal occurs in the face of unchanged muscle glucose-6-phosphate concentrations, this suggest that reduced glucose disposal is secondary to reduced glucose transport in type 1 diabetes.

Diabetes Mellitus, Type 1↗
PubMed1989

Dose-response characteristics for suppression of low molecular weight plasma insulin-like growth factor-binding protein by insulin.

We previously demonstrated that supraphysiological insulin concentrations reduced the plasma 34K insulin-like growth factor-binding protein (IGF-BP) concentrations in humans. In this study we examined whether physiological changes in plasma insulin concentrations regulate IGF-BP and, if so, whether the regulation is influenced by race, glucose tolerance, or rate of glucose metabolism. For these purposes we 1) analyzed the relationship between fasting plasma insulin and IGF-BP concentrations in 2 racial groups (23 caucasians and 35 southwestern American Indians), 2) measured the response of plasma IGF-BP to oral glucose in 20 normal subjects, and 3) determined the dose-response characteristics of plasma IGF-BP to glucose and insulin in 23 normal subjects at 4 different insulin and glucose concentrations. The fasting plasma insulin concentration was inversely related to the plasma IGF-BP concentration in both the caucasian and Indian groups (P less than 0.0001). In the caucasian group the mean plasma IGF-BP concentration was higher [15 +/- 4 (+/- SE) micrograms/L] than in the Indian group (8 +/- 2 micrograms/L; P less than 0.05). This difference was independent of race and glucose tolerance, and it could be explained by lower plasma insulin concentrations in the caucasian (387 +/- 50 pmol/L) than in the Indian group (215 +/- 43 pmol/L; P less than 0.001). After oral glucose administration, the insulin concentration (423 +/- 72 pmol/L) was maximal 30 min after glucose treatment, and significant suppression of the IGF-BP concentration occurred at 90 min. Analysis of the dose-response curves revealed maximal suppression of IGF-BP at about 1150 pmol/L insulin, and half-maximal suppression at about 290 pmol/L. The plasma glucose concentration or the rate of glucose metabolism had no effect on the IGF-BP concentration. These data suggest that insulin is a major regulator of plasma IGF-BP concentrations under physiological conditions.

Adult↗
PubMed1989

Prolonged exercise increases serum insulin-like growth factor-binding protein concentrations.

We studied the response of serum 34K insulin-like growth factor-binding protein (IGF-BP) to two types of prolonged exercise. In the first study, 11 normal men performed cycle ergometer exercise, after an overnight fast, for 3 h at the intensity corresponding to 45-50% of their maximal aerobic power. After the exercise, the mean serum IGF-BP concentration was 4.9-fold higher than the baseline level (P less than 0.01), while the IGF-I concentration did not change. Resting for the same time period resulted in a 38% fall in the serum IGF-BP level (P less than 0.01). In the second study, 10 normal men and 8 type 1 diabetic men exercised, on the average, for 7.5 h in a 75-km cross-country ski race. The mean serum IGF-BP concentration increased 5.4-fold (P less than 0.01) in the normal men and 4.2-fold (P less than 0.01) in the diabetic men. The serum IGF-I concentration decreased by 19% and 21% in the normal and diabetic men, respectively (P less than 0.01). After completion of the ski race, the serum insulin and IGF-BP levels (r = -0.70; P less than 0.05), and serum IGF-I and IGF-BP levels (r = -0.72; P less than 0.05) were inversely correlated in the normal men. No such correlations were found in the diabetic men. We conclude that 1) long term exercise increases serum IGF-BP concentrations in both normal and type 1 diabetic men; and 2) the increases are inversely related to alterations in serum IGF-I and insulin concentrations in normal men. These data suggest that IGF-BP may be involved in regulation of the biological action of IGF-I during prolonged exercise.

Adult↗
PubMed1989

Severity, duration, and mechanisms of insulin resistance during acute infections.

Acute infections provoke insulin resistance. These experiments were designed to study the severity, duration, and mechanisms of insulin resistance caused by acute infections. First, we studied eight patients [mean age, 29 +/- 11 (+/- SD) yr; body mass index, 23 +/- 2 kg/m2] with acute viral or bacterial infections during the acute stage of their infection and 1-3 months after recovery. The rate of glucose infusion required to maintain normoglycemia during hyperinsulinemia (approximately 500 pmol/L) was used as a measure of insulin action. During infection, the glucose requirements in the patients [21 +/- 2 (+/- SE) mumol/kg.min] were 52% less than those in weight- and age-matched normal subjects (44 +/- 2 mumol/kg.min; P less than 0.001). Compared to data from a large group of normal subjects, the resistance to insulin during infection corresponded to that predicted for a weight-matched 84-yr-old normal person or an age-matched obese person with a body mass index of 37 kg/m2. One to 3 months after recovery, the patients' glucose requirements were still significantly lower (37 +/- 3 mumol/kg.min; P less than 0.02) than those in matched normal subjects. To assess the mechanism of insulin resistance, seven additional patients were studied during the acute stage of infection using a low dose insulin infusion (plasma insulin, 215 pmol/L) combined with a [3-3H]glucose infusion and indirect calorimetry. Again, the glucose requirements were 59% lower in the patients (14 +/- 2 mumol/kg.min) than in matched normal subjects (34 +/- 2 mumol/kg.min; P less than 0.001). This decrease was due to a defect in glucose utilization (18 +/- 2 vs. 37 +/- 1 mumol/kg.min; P less than 0.001, patients vs. normal subjects) rather than impaired suppression of glucose production (4 +/- 1 vs. 3 +/- 1 mumol/kg.min, respectively). Total carbohydrate oxidation rates were similar in both groups (16 +/- 2 vs. 14 +/- 1 mumol/kg.min, respectively), whereas the apparent glucose storage was neglible in the patients (2 +/- 1 mumol/kg.min) compared to that in normal subjects (22 +/- 2 mumol/kg.min; P less than 0.001). We conclude that acute infections induce severe and long-lasting insulin resistance, which is localized to glucose-utilizing pathways. The rate of carbohydrate oxidation is normal during infections, whereas the rate of nonoxidative glucose disposal, as determined by indirect calorimetry, is nearly zero. The apparent blockade in glucose storage could result from diminished glycogen synthesis, accelerated glycogenolysis, or both.

Adult↗
PubMed1989

Effect of interferon on glucose tolerance and insulin sensitivity.

Many viral infections induce interferon (IFN) production and cause insulin resistance. To examine the causal relationship between IFN and insulin resistance, we injected natural human leukocyte IFN-alpha (3 x 10(6) IU, i.m.) twice overnight in eight healthy subjects and determined oral (OGT) and intravenous (IVGT) glucose tolerance and sensitivity to insulin (287 nmol or 40 mU.m-2.min-1 euglycemic insulin clamp) the following morning. IFN caused mild influenzalike symptoms and induced a rise in circulating glucose, insulin, hydrocortisone (cortisol), growth hormone, and glucagon concentrations (P less than .05-.001). In the OGT test, the area under the glucose curve was 2.6-fold greater (P less than .02), and the disappearance rate of intravenously administered glucose was reduced by 28% (P less than .05) after IFN administration. The impairment in OGT and IVGT occurred despite augmented insulin response. Insulin-stimulated glucose disposal was reduced by 22% (P less than .005), and insulin clearance increased by 18% (P less than .02) after IFN administration. When the insulin-clamp study was repeated in patients with steady-state hyperinsulinemia that was 12% higher (P less than .005) after IFN, the glucose disposal rate was still reduced by 15% (P less than .01). These data indicate that IFN 1) stimulates counterregulatory hormone secretion, 2) impairs glucose tolerance and insulin sensitivity, and 3) stimulates insulin clearance. Thus, IFN may be involved in the development of insulin resistance during viral infections.

Adult↗