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G B Bolli

Publications and source records attributed to G B Bolli.

At least 19 recordsLinked to original sources
PubMed2006

Effect of the amino acid alanine on glucagon secretion in non-diabetic and type 1 diabetic subjects during hyperinsulinaemic euglycaemia, hypoglycaemia and post-hypoglycaemic hyperglycaemia.

AIMS/HYPOTHESIS: The aim of our study was to establish whether the well-known defective or absent secretion of glucagon in type 1 diabetes in response to hypoglycaemia is selective or includes lack of responses to other stimuli, such as amino acids. MATERIALS AND METHODS: Responses of glucagon to hypoglycaemia were measured in eight patients with type 1 diabetes and six non-diabetic subjects during hyperinsulinaemic (insulin infusion 0.5 mU kg(-1) min(-1)) and eu-, hypo- and hyperglycaemic clamp studies (sequential steps of plasma glucose 5.0, 2.9, 5.0, 10 mmol/l). Subjects were studied on three randomised occasions with infusion of low- or high-dose alanine, or saline. RESULTS: With saline, glucagon increased in hypoglycaemia in non-diabetic subjects but not in diabetic subjects. Glucagon increased further with low-dose (181 +/- 16 ng l(-1) min(-1)) and high-dose alanine (238 +/- 20 ng l(-1) min(-1)) in non-diabetic subjects, but only with high-dose alanine in diabetic subjects (area under curve 112 +/- 5 ng l(-1) min(-1)). The alanine-induced glucagon increase in diabetic subjects paralleled the spontaneous glucagon response to hypoglycaemia in non-diabetic subjects not receiving alanine. The greater responses of glucagon to hypoglycaemia with alanine infusion were offset by recovery of eu- or hyperglycaemia. CONCLUSIONS/INTERPRETATION: In type 1 diabetes, the usually deficient responses of glucagon to hypoglycaemia may improve after increasing the concentration of plasma amino acids. Amino acid-enhanced secretion of glucagon in response to hypoglycaemia remains under physiological control since it is regulated primarily by the ambient plasma glucose concentration. These findings might be relevant to improving counter-regulatory defences against insulin-induced hypoglycaemia in type 1 diabetes.

Adolescent↗
PubMed2006

Glucagon: the effects of its excess and deficiency on insulin action.

AIM: To review the role that glucagon plays in physiology, physiopathology and clinical medicine. DATA SYNTHESIS: Glucagon assays employing specific radioimmunoassay (RIA) techniques are now widely used to characterize pathologic conditions where the effect of the excess or deficiency of glucagon on insulin actions might play a role. Glucagon excess counteracts the action of insulin on glucose metabolism by stimulating glycogenolysis and gluconeogenesis. Aside from glucagon excess in association with glucagonoma, glucagon excess is found in several metabolic disturbances. In diabetes mellitus, hyperglycaemia is the consequence of the glycogenolytic and gluconeogenic effects of glucagon excess occurring in the setting of a relative insulin deficiency (i.e. Type 2 diabetes), whereas excess of glucagon and absent insulin levels are typical features of diabetic ketoacidosis. Although plasma glucagon levels of patients with diabetes are usually increased relative to the prevailing plasma glucose concentrations, it is a paradox that in those patients glucagon levels fail to rise when hypoglycaemia develops. Since glucagon release is considered the primary defence against insulin-induced hypoglycaemia, the defective response of glucagon to hypoglycaemia may favour the development of severe hypoglycaemia. Such defective response to hypoglycaemia in diabetes can be regarded as a condition of selective glucagon deficiency the mechanisms of which remain to be elucidated. CONCLUSION: The most common condition associated with glucagon excess or deficiency is diabetes mellitus. Glucagon excess contributes to hyperglycaemia whereas reduced glucagon response to insulin-induced hypoglycaemia promotes severe hypoglycaemia. It is expected that drugs that are able to reduce glucagon secretion in concert with strategies directed to recover glucagon secretion to hypoglycaemia might contribute to improve the overall glycaemic control in diabetes.

Blood Glucose↗
PubMed2006

Evaluation of the accuracy of a microdialysis-based glucose sensor during insulin-induced hypoglycemia, its recovery, and post-hypoglycemic hyperglycemia in humans.

BACKGROUND: These studies were designed to evaluate the accuracy of a microdialysis-based subcutaneous glucose sensor (GlucoDay, A. Menarini Diagnostics, Firenze, Italy) compared with a standard reference method of plasma glucose measurement during insulin-induced hypoglycemia. RESEARCH DESIGN AND METHODS: Nine subjects without diabetes were studied in eu-, hypo-, and hyperglycemia (clamp technique). The GlucoDay was calibrated against one arterialized plasma glucose measurement (Glucose Analyzer, Beckman, Brea, CA), and plasma glucose estimates every 3 min were compared with paired plasma glucose values. RESULTS: Accuracy of glucose estimates was not homogeneously distributed among subjects and depended on stability of the sensor's current signal during spontaneous euglycemia (R +/- -0.68). Linear regression analysis showed a good correlation between the two methods of measurement (R = 0.9), Deming regression showed the inclusion of the unit in the confidence interval of the slope (slope 0.95, 95% confidence interval 0.87-1.02), and the accuracy of the GlucoDay reached 40 +/- 15% (American Diabetes Association criteria). The mean relative difference was 6 +/- 8% in euglycemia, 13 +/- 14% during plasma glucose fall, 5 +/- 22% in the hypoglycemic plateau, and -14 +/- 16% during recovery from hypoglycemia. The Bland-Altman analysis indicated a bias of -1.9 +/- 16.6 mg/dL, whereas the Error Grid Analysis showed 94% of the Gluco- Day measurements in the acceptable zones of the grid. The time to reach the glycemic nadir was longer when measured with the GlucoDay (90 +/- 5 vs. 72.5 +/- 9 min, P < 0.05). However, absolute values of glycemic nadir, time spent in hypoglycemia, and the rate of fall of glycemia and the rate of recovery from the hypoglycemia were not statistically different. CONCLUSIONS: GlucoDay closely monitors changes in plasma glucose before, during, and after hypoglycemia. However, these results can be achieved only if calibration of the GlucoDay is performed under conditions of sensor signal stability. Similar studies have to be performed in subjects with diabetes to validate the GlucoDay system.

Adult↗
PubMed2006

Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial.

AIMS: The goal of the study was to determine whether continuous subcutaneous insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen based on neutral protamine hagedorn (NPH) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes. METHODS: The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11 European centres. Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period, respectively. The quality of glycaemic control was assessed by HbA(1c), blood glucose values, and the frequency of hypoglycaemic events. For the evaluation of the quality of life, three different self-report questionnaires have been assessed. RESULTS: CSII treatment resulted in lower HbA(1c) (7.45 vs. 7.67%, P < 0.001), mean blood glucose level (8.6 vs. 9.4 mmol/l, P < 0.001) and less fluctuation in blood glucose levels than MDI (+/- 3.9 vs. +/- 4.3 mmol/l, P < 0.001). There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI, with an incidence ratio of 1.12 [95% confidence interval (CI): 1.08-1.17] and 2.61 (95% CI: 1.59-4.29) for mild and severe hypoglycaemia, respectively. The overall score of the diabetes quality of life questionnaire was higher for CSII (P < 0.001), and an improvement in pump users' perception of mental health was detected when using the SF-12 questionnaire (P < 0.05). CONCLUSION: CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes, with improvement in all significant metabolic parameters as well as in patients' quality of life. Additional studies are needed to compare CSII with glargine- and detemir-based MDI.

Adult↗
PubMed2004

Effects of whole-body vibration exercise on the endocrine system of healthy men.

Whole-body vibration is reported to increase muscle performance, bone mineral density and stimulate the secretion of lipolytic and protein anabolic hormones, such as GH and testosterone, that might be used for the treatment of obesity. To date, as no controlled trial has examined the effects of vibration exercise on the human endocrine system, we performed a randomized controlled study, to establish whether the circulating concentrations of glucose and hormones (insulin, glucagon, cortisol, epinephrine, norepinephrine, GH, IGF-1, free and total testosterone) are affected by vibration in 10 healthy men [age 39 +/- 3, body mass index (BMI) of 23.5 +/- 0.5 kg/m2, mean +/- SEM]. Volunteers were studied on two occasions before and after standing for 25 min on a ground plate in the absence (control) or in the presence (vibration) of 30 Hz whole body vibration. Vibration slightly reduced plasma glucose (30 min: vibration 4.59 +/- 0.21, control 4.74 +/- 0.22 mM, p=0.049) and increased plasma norepinephrine concentrations (60 min: vibration 1.29 +/- 0.18, control 1.01 +/- 0.07 nM, p=0.038), but did not change the circulating concentrations of other hormones. These results demonstrate that vibration exercise transiently reduces plasma glucose, possibly by increasing glucose utilization by contracting muscles. Since hormonal responses, with the exception of norepinephrine, are not affected by acute vibration exposure, this type of exercise is not expected to reduce fat mass in obese subjects.

Adult↗
PubMed2004

Better long-term glycaemic control with the basal insulin glargine as compared with NPH in patients with Type 1 diabetes mellitus given meal-time lispro insulin.

BACKGROUND: Glargine is a long-acting insulin analogue potentially more suitable than NPH insulin in intensive treatment of Type 1 diabetes mellitus (T1 DM), but no study has proven superiority. The aim of this study was to test superiority of glargine on long-term blood glucose (BG) as well as on responses to hypoglycaemia vs. NPH. METHODS: One hundred and twenty-one patients with T1 DM on intensive therapy on four times/day NPH and lispro insulin at each meal, were randomized to either continuation of NPH four times/day (n = 60), or once daily glargine at dinner-time (n = 61) for 1 year. Lispro insulin at meal-time was continued in both groups. In 11 patients from each group, responses to stepped hyperinsulinaemic-hypoglycaemia were measured before and after 1 year's treatment. RESULTS: Mean daily BG was lower with glargine [7.6 +/- 0.11 mmol/l (137 +/- 2 mg/dl)] vs. NPH [8.1 +/- 0.22 mmol/l (146 +/- 4 mg/dl)] (P < 0.05). HbA(1c) at 4 months did not change with NPH, but decreased with glargine (from 7.1 +/- 0.1 to 6.7 +/- 0.1%), and remained lower than NPH at 12 months (6.6 +/- 0.1%, P < 0.05 vs. NPH). Frequency of mild hypoglycaemia [self-assisted episodes, blood glucose < or = 4.0 mmol/l (72 mg/dl)] was lower with glargine vs. NPH (7.2 +/- 0.5 and 13.2 +/- 0.6 episodes/patient-month, P < 0.05). After 1 year, NPH treatment resulted in no change of responses to hypoglycaemia, whereas with glargine plasma glucose, thresholds and maximal responses of plasma adrenaline and symptoms to hypoglycaemia improved (P < 0.05). CONCLUSIONS: The simpler glargine regimen decreases the percentage of HbA(1c) and frequency of hypoglycaemia and improves responses to hypoglycaemia more than NPH. Thus, glargine appears more suitable than NPH as basal insulin for intensive treatment of T1 DM.

Adult↗
PubMed2002

Rate of fall of blood glucose and physiological responses of counterregulatory hormones, clinical symptoms and cognitive function to hypoglycaemia in Type I diabetes mellitus in the postprandial state.

AIMS/HYPOTHESIS: The aim of this study was to establish the effect of a rate of decreasing plasma glucose concentrations on responses to hypoglycaemia, i.e. release of counterregulatory hormones, perception of symptoms, deterioration of cognitive function, and rates of forearm noradrenaline spillover, in the postprandial condition and in the sitting position. METHODS: We studied 11 subjects with Type I (insulin-dependent) diabetes mellitus, twice during clamped insulin-induced hypoglycaemia (2.4 mmol/l) after eating in the sitting position. On one occasion, plasma glucose was decreased at the rate of 0.1+/-0.003 mmol x min(-1) x l(-1) (fast fall), on the other at the rate of 0.03+/-0.001 mmol x min(-1) x l(-1) (slow fall). Subjects underwent a control euglycaemic clamp study as well. RESULTS: In response to fast-fall as compared to slow-fall hypoglycaemia, which was about 30 min longer, cognitive tasks were performed as follows: Trail-Making B, PASAT 2 s, Digit Vigilance Test and Verbal Memory deteriorated more, adrenaline increased less (2.8+/-0.5 vs 3.5+/-0.7 nmol/l, p=0.03), forearm noradrenaline spillover was greater (6.5+/-1.0 vs 5.2+/-0.4 pmol x min(-1) x 100 ml(-1), p=0.04), and symptoms were no different. After recovery from hypoglycaemia, cognitive function was still deteriorated compared to the baseline with no difference between fast and slow-fall hypoglycaemia. The evident response of glucagon to postprandial hypoglycaemia contrasted with the blunted or absent response in the fasting state. CONCLUSION/INTERPRETATION: In the postprandial condition and sitting position, fast-fall hypoglycaemia is more dangerous than slow-fall, because it deteriorates cognitive function more, and activates responses of counterregulatory hormones less than slow-fall hypoglycaemia.

Adult↗
PubMed2002

Basal-bolus insulin therapy in Type 1 diabetes: comparative study of pre-meal administration of a fixed mixture of insulin lispro (50%) and neutral protamine lispro (50%) with human soluble insulin.

AIMS: To ascertain whether pre-meal administration of 50% insulin lispro and 50% neutral protamine lispro (NPL), given as a fixed mixture (Humalog Mix50, human soluble (regular) insulin as a basal-bolus regimen in people with Type 1 diabetes. Both regimens included bedtime human isophane (NPH) insulin. METHODS: This was a multinational, multicentre, randomized, open-label, two-period crossover comparison of two insulin treatments for two 12-week periods in 109 patients with Type 1 diabetes. The protocol provided preliminary evaluations of dose requirements and recommendations for insulin dose adjustment when switching regimens on the basis of blood glucose (BG) values. Eight-point BG profiles, frequency of hypoglycaemia, HbA1c, insulin dose, time of injection, and frequency of snacking were assessed during each treatment. RESULTS: Total daily insulin dose was similar for both treatments, but the total pre-meal doses were higher (P < 0.001) and the bedtime dose of isophane was lower (P < 0.001) with Mix50. The pre-meal dose before breakfast and lunch, although statistically different (P = 0.006 and P < 0.001, respectively), was of similar magnitude, but the pre-evening meal dose was higher with Mix50 (P < 0.001). Median (interquartile range) time of insulin injection before meals was: Mix50 4.2 (25th percentile = 1.0; 75th percentile = 6.3) min, human soluble insulin 24.6 (25th percentile = 16.6; 75th percentile = 30.0) min. Pre-meal and bedtime BG concentrations did not differ between treatments. The BG 2 h after the evening meal was lower with Mix50 (8.40 +/- 2.95 mmol/l vs. 9.60 +/- 3.47 mmol/l) (P = 0.049). BG after breakfast and lunch, mean HbA1c, frequency of hypoglycaemia, frequency of snacks, and body weight were not different. CONCLUSION: The use of Mix50 in a basal-bolus regimen achieved similar control of pre-meal BG to human soluble insulin, and overall glycaemic control and hypoglycaemia risk were equivalent. This suggests that Mix50 can provide an adequate supply of insulin to control BG between meals while providing the convenience of injecting immediately before meals.

Adult↗
PubMed2001

Insulins today and beyond.

The advent of insulin almost 80 years ago revolutionised treatment of diabetes and must be one of the most outstanding achievements of twentieth century medicine. Since then, there has been an ever-increasing awareness and acceptance of the need to achieve and sustain near-normoglycaemia to delay onset and retard progression of diabetic angiopathy. Physiological insulin replacement is therefore central to management of patients with diabetes who are unable to make [corrected] insulin. Insulin formulations, treatment strategies, and methods and routes of delivery have changed much, with more and more options for monitoring the effect on blood glucose concentrations. Patients with type 1 and type 2 diabetes need insulin much more aggressively than previously. Parallel developments in glucose-sensing technologies are welcomed as an integral part of safe and optimum implementation of insulin replacement therapy.

Absorption↗
PubMed2001

Physiological insulin replacement in type 1 diabetes mellitus.

The DCCT and UKPDS studies have definitely established that in type 1 as well as in type 2 diabetes mellitus, long-term near-normoglycaemia strongly protects against onset and/or progression of microangiopathic complications. Therefore, implementation of insulin strategies to maintain long-term near-normoglycaemia is of key importance in the management of diabetes mellitus. To successfully reach the goal of near-normoglycaemia, insulin therapy has to be physiological, i.e. it has to mimic nature by providing a bolus of insulin at meal ingestion, and by replacing the need for basal insulin between meals and during the night. The meal-time insulin needs can be best met by s.c. injection of a short-acting insulin analogue (lispro, aspart). Short-acting insulin analogues should be preferred to human regular insulin for three main reasons. First, convenience (meal-time injection, better adaptation of insulin dose to carbohydrate content of the meal); second, lower blood glucose 2-hour after meals; third, less risk for late post-prandial hypoglycaemia. However, the benefits of meal-time treatment with short-acting insulin analogues become apparent only by the extent to which replacement of basal insulin is optimised as well. The interprandial (especially nocturnal) need for basal insulin can be best met by the continuous s.c. insulin infusion by an external minipump, the gold standard of basal insulin replacement. Continuous s.c. insulin infusion in the basal state is so good because it uses a short-acting insulin analogue (low variability in s.c. absorption, flat and peak-less action profile), not insulin preparations with retarded action (high variability of s.c. absorption, peak of action) likewise the model of multiple daily insulin injections. A second choice option is s.c. injection of an insulin preparation with retarded action. At present, the long-acting insulin analogue glargine is the retarded insulin preparation of choice because its action profile is flat, peakless and long-lasting (approximately 24 hours). This is in contrast with the peak action profile of NPH insulin which exhibits a short duration of action (10-15 h). Thus, the modern insulin strategies for intensive therapy always include use of a short-acting insulin analogue at meal-time, and use of either continuous s.c. insulin infusion, or a s.c. injection of insulin glargine to replace basal insulin. Insulin glargine reproduces closely the pharmacokinetics and pharmacodynamics of continuous s.c. insulin infusion, and should always be preferred to NPH in all insulin-requiring diabetic patients, both type 1 and type 2.

Blood Glucose↗
PubMed2001

Intensive insulin treatment in diabetic children.

Intensification of insulin therapy which maintains long-term near-normoglycaemia (HbA1c<7.0%) strongly protects against onset and/or progression of diabetic microangiopathy in Type 1 diabetes mellitus of adults. Similar intensification of insulin therapy is needed in diabetic children as well, in order to prevent complications a few years after diabetes onset, ie very often in young age. Provided adequate psychosocial support and education are available, children should be treated with multiple daily injections of insulin or, when necessary, with continuous subcutaneous insulin infusion, along with blood glucose monitoring. Insulin regimens may differ from child to child and vary from day to day in the same child, depending on lifestyle and considering all the available insulin preparations. These include the short-acting insulin (both human regular and short-acting insulin analogues), the intermediate-acting insulin (NPH and Lente), as well as the new long-acting insulin analogue glargine. The latter seems a promising candidate to substitute of basal insulin. The concern that intensified insulin therapy increases the risk of hypoglycaemia, as indicated by the Diabetes Control and Complications Trial (DCCT), is no longer tenable. On the contrary, a physiological, flexible insulin regimen better than a fixed insulin regimen, usually the twice daily split-mixed regimen, protects against the risk of hypoglycaemia in relation to food ingestion, physical exercise and sleep. Thus, appropriate education should be delivered at diabetes onset to the child and parents in order to start the strategy of intensified insulin therapy as early as possible.

Blood Glucose↗
PubMed2000

Insulin glargine.

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Blood Glucose↗
PubMed2000

Autoantibody recognition of COOH-terminal epitopes of GAD65 marks the risk for insulin requirement in adult-onset diabetes mellitus.

Some type 2 diabetic subjects develop secondary failure to sulphonylurea treatment and require insulin therapy. To test the diagnostic sensitivity and specificity of epitopes of GAD65 autoantibodies (GAD65Ab) for insulin requirement, in patients with latent autoimmune diabetes of the adult, we studied 569 adult subjects with a clinical diagnosis of type 2 diabetes mellitus. All the patients had been initially treated with hypoglycemic agents and/or diet for at least 1 yr. The presence of GAD65Ab (61/569, 10.7%) depended on insulin therapy (P<0.0001), low BMI (P<0.0001), and low basal C-peptide (P = 0.01). The majority of GAD65Ab-positive subjects (47/61, 77%) had antibodies directed to both middle (GAD65-MAb) and COOH-terminal (GAD65-CAb) epitopes. However, GAD65-CAb were more frequent in insulin-treated subjects (92% of GAD65Ab+ individuals) than in subjects treated with hypoglycemic agents and/or diet (18.2% of GAD65Ab+ individuals), while the exclusive presence of GAD65-MAb was more frequent in subjects treated with hypoglycemic agents and/or diet (81.8% vs. 8%) (P<0.0001). The presence of GAD65-CAb had a diagnostic specificity for insulin requirement as high as 99.4% (compared with 96.9% of GAD65Ab as measured in the traditional radiobinding assay) and identified a subgroup of patients with low BMI, low basal C-peptide values, and a need for insulin therapy. Subjects carrying only GAD65-MAb were phenotypically indistinguishable from GAD65Ab-negative patients. Patients positive for GAD65-M+CAb, but not those positive for GAD65-MAb only, showed an increased risk for thyroid autoimmunity, as revealed by the presence of thyroid peroxidase autoantibodies. Our study demonstrates that the use of epitope-specific antibody assays improves the diagnostic specificity of GAD65Ab, and that the presence of GAD65Ab binding to COOH-terminal epitopes is strongly associated with a need for insulin requirement.

Adult↗
PubMed2000

Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro.

To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide-negative type 1 diabetic patients were studied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U x kg(-1) x 24 h(-1)) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of IV insulin >50%) was earlier with NPH (0.8 +/- 0.2 h), CSII (0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus glargine (1.5 +/- 0.3 h) (P < 0.05) (mean +/- SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 +/- 4 h) than with NPH (14 +/- 3 h) (P < 0.05) but was similar with ultralente (20 +/- 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed by waning, whereas glargine had no peak but had a flat concentration/action profile mimicking CSII. Interindividual variability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultralente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mimics CSII, the gold standard of basal insulin replacement.

Adult↗
PubMed2000

Enhanced stimulation of glucose uptake by insulin increases exercise-stimulated glucose uptake in skeletal muscle in humans: studies using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography.

In vitro studies have shown that insulin and exercise stimulate glucose uptake in part via distinct mechanisms. We determined whether a high rate of insulin-stimulated glucose uptake (good insulin sensitivity) is associated with an enhanced ability of exercise to increase glucose uptake in vivo in humans. In our study, 22 normal subjects performed one-legged isometric exercise for 105 min (45-150 min) under intravenously maintained euglycemic-hyperinsulinemic conditions (0-150 min). Rates of oxygen consumption, blood flow, and glucose uptake were quantitated simultaneously in skeletal muscle of both legs using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography. The one-legged exercise, performed at an intensity of 11% of maximal isometric force, was designed to induce similar increases in oxygen consumption in both groups. In the entire group, exercise increased oxygen consumption from 2.3 +/- 0.3 ml x kg(-1) muscle x min(-1) (insulin) to 34.2 +/- 3. ml x kg(-1) muscle x min(-1) (insulin and exercise) (P < 0.001) and muscle glucose uptake from 60 +/- 6 pmol x kg(-1) muscle x min(-1) (insulin) to 220 +/- 22 micromol x kg(-1) muscle x min(-1) (insulin and exercise) (P < 0.001). The exercise-induced increase in glucose uptake was due to marked increases in blood flow (36 +/- 5 ml x kg(-1) muscle x min(-1) [insulin] vs. 262 +/- 20 ml x kg(-1) muscle x min(-1) [insulin and exercise], P < 0.001) rather than glucose extraction, which decreased from 2.0 +/- 0.2 mmol/l (insulin) to 1.0 +/- 0.1 mmol/1 (insulin and exercise) (P < 0.001). The subjects were classified according to their mean rate of whole-body insulin-stimulated glucose uptake into those with high (49 +/- 3 micromol x kg(-1) x min(-1)) and normal (27 +/- 2 micromol x kg(-1) x min(-1)) rates of insulin-stimulated glucose uptake. Both insulin-stimulated (2.4 +/- 1.1 vs. 2.3 +/- 1.2 ml x kg(-1) muscle x min(-1), normal vs. high insulin sensitivity) and exercise- and insulin-stimulated (33 +/- 6 vs. 34 +/- 4 ml x kg(-1) muscle x min(-1)) rates of oxygen consumption were comparable between the groups. Exercise increased glucose uptake more in the group with high insulin sensitivity (195 +/- 25 pmol x kg(-1) muscle x min(-1)) than in the group with normal insulin sensitivity (125 +/- 19 micromol x kg(-1) muscle x min(-1)) (P < 0.05). Muscle blood flow was closely correlated with the rate of oxygen consumption (r = 0.91, P < 0.0001), and insulin-stimulated (30 +/- 5 vs. 35 +/- 6 ml x kg(-1) muscle x min(-1)) and exercise-induced increments (222 +/- 31 vs. 228 +/- 23 ml x kg(-1) muscle x min(-1)) in muscle blood flow were similar between the groups. Glucose extraction remained higher in the group with high insulin sensitivity (1.2 +/- 0.2 mmol/l) than in the group with normal insulin sensitivity (0.7 +/- 0.1 mmol/l, P < 0.05). We conclude that whereas acute exercise per se increases glucose uptake via increasing glucose delivery, good insulin sensitivity modulates exercise-induced increases in glucose uptake by enhancing cellular glucose extraction.

Adult↗