Effects of creatine supplementation on glucose tolerance and insulin sensitivity in sedentary healthy males undergoing aerobic training

Recent findings have indicated that creatine supplementation may affect glucose metabolism. This study aimed to examine the effects of creatine supplementation, combined with aerobic training, on glucose tolerance in sedentary healthy male. Subjects (n = 22) were randomly divided in two groups and were allocated to receive treatment with either creatine (CT) ( approximately 10 g . day over three months) or placebo (PT) (dextrose). Administration of treatments was double blind. Both groups underwent moderate aerobic training. An oral glucose tolerance test (OGTT) was performed and both fasting plasma insulin and the homeostasis model assessment (HOMA) index were assessed at the start, and after four, eight and twelve weeks. CT demonstrated significant decrease in OGTT area under the curve compared to PT (P = 0.034). There were no differences between groups or over time in fasting insulin or HOMA. The results suggest that creatine supplementation, combined with aerobic training, can improve glucose tolerance but does not affect insulin sensitivity, and may warrant further investigation with diabetic subjects.     

Metabolic response to insulin induced hypoglycaemia in lean and obese subjects

Metabolic response to insulin induced hypoglycaemia was examined in 8 lean and 11 obese subjects. The metabolic rate increased in lean and obese subjects during the hypoglycaemia. The mean response (as the sum of all the values above basal) was not significantly different between lean and obese subjects. The mean decrease in blood glucose and the mean hormonal response (increase in cortisol, adrenaline and noradrenaline) were not different between lean subjects and obese subjects. However, the metabolic response and noradrenaline response were variable in obese subjects and some obese subjects showed a poor response. These results suggest that in some obese subjects, there may be reduced thermogenic response to insulin induced hypoglycaemia.     

Effects of fasting on insulin action and glucose kinetics in lean and obese men and women

The development of insulin resistance in the obese individual could impair the ability to appropriately adjust metabolism to perturbations in energy balance. We investigated a 12- vs. 48-h fast on hepatic glucose production (R(a)), peripheral glucose uptake (R(d)), and skeletal muscle insulin signaling in lean and obese subjects. Healthy lean [n = 14; age = 28.0 +/- 1.4 yr; body mass index (BMI) = 22.8 +/- 0.42] and nondiabetic obese (n = 11; age = 34.6 +/- 2.3 yr; BMI = 36.1 +/- 1.5) subjects were studied following a 12- and 48-h fast during 2 h of rest and a 3-h 40 mUxm(-2)xmin(-1) hyperinsulinemic-euglycemic clamp (HEC). Basal glucose R(a) decreased significantly from the 12- to 48-h fast (lean 1.96 +/- 0.23 to 1.63 +/- 0.15; obese 1.23 +/- 0.07 to 1.07 +/- 0.07 mgxkg(-1)xmin(-1); P = 0.004) and was equally suppressed during the HEC after both fasts. The increase in glucose R(d) during the HEC after the 12-h fast was significantly decreased in lean and obese subjects after the 48-h fast (lean 9.03 +/- 1.17 to 4.16 +/- 0.34, obese 6.10 +/- 0.77 to 3.56 +/- 0.30 mgxkg FFM(-1)xmin(-1); P < 0.001). After the 12- but not the 48-h fast, insulin-stimulated AKT Ser(473) phosphorylation was greater in lean than obese subjects. We conclude that 1) 48 h of fasting produces a marked decline in peripheral insulin action, while suppression of hepatic glucose production is maintained in lean and obese men and women; and 2) the magnitude of this decline is greater in lean vs. obese subjects.     

Effect of exercise training on insulin sensitivity and glucose metabolism in lean, obese, and diabetic men.

To clarify the impact of vigorous physical training on in vivo insulin action and glucose metabolism independent of the intervening effects of concomitant changes in body weight and composition and residual effects of an acute exercise session, 10 lean, 10 obese, and 6 diet-controlled type II diabetic men trained for 12 wk on a cycle ergometer 4 h/wk at approximately 70% of maximal O2 uptake (VO2max) while body composition and weight were maintained by refeeding the energy expended in each training session. Before and 4-5 days after the last training session, euglycemic hyperinsulinemic (40 mU.m2.min-1) clamps were performed at a plasma glucose of 90 mg/dl, combined with indirect calorimetry. Total insulin-stimulated glucose disposal (M) was corrected for residual hepatic glucose output. Body weight, fat, and fat-free mass (FFM) did not change with training, but cardiorespiratory fitness increased by 27% in all groups. Before and after training, M was lower for the obese (5.33 +/- 0.39 mg.kg FFM-1.min-1 pretraining; 5.33 +/- 0.46 posttraining) than for the lean men (9.07 +/- 0.49 and 8.91 +/- 0.60 mg.kg FFM-1.min-1 for pretraining and posttraining, respectively) and lower for the diabetic (3.86 +/- 0.44 and 3.49 +/- 0.21) than for the obese men (P less than 0.001). Insulin sensitivity was not significantly altered by training in any group, but basal hepatic glucose production was reduced by 22% in the diabetic men. Thus, when intervening effects of the last exercise bout or body composition changes were controlled, exercise training per se leading to increased cardiorespiratory fitness had no independent impact on insulin action and did not improve the insulin resistance in obese or diabetic men.     

Effects of fructose and glucose on plasma leptin, insulin, and insulin resistance in lean and VMH-lesioned obese rats

To determine the influence of dietary fructose and glucose on circulating leptin levels in lean and obese rats, plasma leptin concentrations were measured in ventromedial hypothalamic (VMH)-lesioned obese and sham-operated lean rats fed either normal chow or fructose- or glucose-enriched diets (60% by calories) for 2 wk. Insulin resistance was evaluated by the steady-state plasma glucose method and intravenous glucose tolerance test. In lean rats, glucose-enriched diet significantly increased plasma leptin with enlarged parametrial fat pad, whereas neither leptin nor fat-pad weight was altered by fructose. Two weeks after the lesions, the rats fed normal chow had marked greater body weight gain, enlarged fat pads, and higher insulin and leptin compared with sham-operated rats. Despite a marked adiposity and hyperinsulinemia, insulin resistance was not increased in VMH-lesioned rats. Fructose brought about substantial insulin resistance and hyperinsulinemia in both lean and obese rats, whereas glucose led to rather enhanced insulin sensitivity. Leptin, body weight, and fat pad were not significantly altered by either fructose or glucose in the obese rats. These results suggest that dietary glucose stimulates leptin production by increasing adipose tissue or stimulating glucose metabolism in lean rats. Hyperleptinemia in VMH-lesioned rats is associated with both increased adiposity and hyperinsulinemia but not with insulin resistance. Dietary fructose does not alter leptin levels, although this sugar brings about hyperinsulinemia and insulin resistance, suggesting that hyperinsulinemia compensated for insulin resistance does not stimulate leptin production.     

Effects of oral zinc gluconate on glucose effectiveness and insulin sensitivity in humans

Zinc improves both insulin secretion and insulin sensitivity, and exerts insulin-like effects. We investigated its acute effects on the parameters of glucose assimilation determined with the minimal model technique from frequent sampling intravenous glucose tolerance test (FSIVGTT) in seven healthy volunteers. FSIVGTTs (0.5 g/kg of glucose, followed by 2 U insulin iv injection at 19 min) were performed after the subjects had taken 20 mg zinc gluconate twice (the evening before and 30 min before the beginning of the test) or placebo pills (simple blind randomized protocol). Glucose assimilation was analyzed by calculating Kg (slope of the exponential decrease in glycemia), glucose effectiveness Sg (i.e., ability of glucose itself to increase its own disposal independent of insulin response), and SI (insulin sensitivity, i.e. the effect of increases in insulinemia on glucose disposal). The two latter parameters were calculated by fitting the experimental data with the two equations of Bergman’s “minimal model”. Zinc increased Kg (p<0.05) and Sg (p<0.05), whereas SI and insulin first-phase secretion did not significantly increase. This study suggests that zinc improves glucose assimilation, as evidenced by the increase in Kg, and that this improvement results mainly from an increase in glucose effectiveness (insulin-like effect), rather than an action on insulin response or insulin sensitivity.     

Blood glucose and serum insulin levels in lean and genetically obese mice.

Fed and 24 hour fasted lean and genetically obese mice (ob/ob) were given a fixed glucose load per gm body weight by intraperitoneal and intragastric administration. Intraperitoneal glucose injection into the obese mice produced a prolonged elevated blood glucose level with a concomitant significant decrease of circulating insulin. Possible interpretations of this observation are discussed. In those obese animals in which glucose was administered intragastrically the fed obese mice had a blood glucose concentration of 450-500 mg% for a period of one hour but there was no increase in circulating insulin, however, in the fasted obese mice in which the glucose concentration was about 350 mg% for one hour, there was a significant increase in the circulating insulin levels. The fed and fasted lean mice showed normal glucose tolerance curves and the expected increase in circulating insulin following either intraperitoneal orintragastric glucose loads. It is concluded that hyperglycaemia in the ob/ob mice is unlikely to be the principal cause of hyperinsulinaemia.     

Effects of zinc supplementation on the plasma glucose level and insulin activity in genetically obese (ob/ob) mice

The effects of zinc supplementation (20 mM ZnCl₂ from the drinking water for eight weeks) on plasma glucose and insulin levels, as well as its in vitro effect on lipogenesis and lipolysis in adipocytes were studied in genetically obese (ob/ob) mice and their lean controls (+/?). Zinc supplementation reduced the fasting plasma glucose levels in both obese and lean mice by 21 and 25%, respectively (p < 0.05). Fasting plasma insulin levels were significantly decreased by 42% in obese mice after zinc treatment. In obese mice, zinc supplementation also attenuated the glycemic response by 34% after the glucose load. The insulin-like effect of zinc on lipogenesis in adipocytes was significantly increased by 80% in lean mice. However, the increment of 74% on lipogenesis in obese mice was observed only when the zinc plus insulin treatment was given. This study reveals that zinc supplementation alleviated the hyperglycemia of ob/ob mice, which may be related to its effect on the enhancement of insulin activity.     

Somatostatin response to glucose before and after prolonged fasting in lean and obese non-diabetic subjects

Insulin, glucagon, and somatostatin concentrations were measured in 7 lean and 7 obese non-diabetic subjects over 7 days of fasting. In addition each subject was given a 75 g oral glucose tolerance test after fasts of 12 h and 7 days. In lean subjects complete food deprivation induced a significant decrease in the circulating levels of both insulin and somatostatin, while glucagon nearly doubled by 48 h and then remained constant for the duration of starvation. Refeeding with oral glucose suppressed the increased plasma glucagon, but insulin and somatostatin responses were enhanced in comparison with the prefast values, as assessed by the integrated areas of change. In obese subjects peripheral insulin and somatostatin levels were significantly lowered, but plasma glucagon level was unchanged at the end of the starvation period. In the same group glucose-induced insulin and somatostatin release were greater than in the fed state. Suppression of plasma glucagon by glucose appeared less complete in obese than in lean subjects. It is concluded that prolonged starvation enhances D-cell responsiveness to glucose in lean and obese subjects.     

Effect of antioxidant supplementation on insulin sensitivity in response to endurance exercise training

While production of reactive oxygen and nitrogen species (RONS) is associated with some of the beneficial adaptations to regular physical exercise, it is not established whether RONS play a role in the improved insulin-stimulated glucose uptake in skeletal muscle obtained by endurance training. To assess the effect of antioxidant supplementation during endurance training on insulin-stimulated glucose uptake, 21 young healthy (age 29 ± 1 y, BMI 25 ± 3 kg/m(2)) men were randomly assigned to either an antioxidant [AO; 500 mg vitamin C and 400 IU vitamin E (α-tocopherol) daily] or a placebo (PL) group that both underwent a supervised intense endurance-training program 5 times/wk for 12 wk. A 3-h euglycemic-hyperinsulinemic clamp, a maximal oxygen consumption (Vo(2max)) and maximal power output (P(max)) test, and body composition measurements (fat mass, fat-free mass) were performed before and after the training. Muscle biopsies were obtained for determination of the concentration and activity of proteins regulating glucose metabolism. Although plasma levels of vitamin C (P < 0.05) and α-tocopherol (P < 0.05) increased markedly in the AO group, insulin-stimulated glucose uptake increased similarly in both the AO (17.2%, P < 0.05) and the PL (18.9%, P < 0.05) group in response to training. Vo(2max) and P(max) also increased similarly in both groups (time effect, P < 0.0001 for both) as well as protein content of GLUT4, hexokinase II, and total Akt (time effect, P ≤ 0.05 for all). Our results indicate that administration of antioxidants during strenuous endurance training has no effect on the training-induced increase in insulin sensitivity in healthy individuals.     

Effects of growth hormone therapy on glucose metabolism and insulin sensitivity indices in prepubertal children with Prader-Willi syndrome

In Prader-Willi syndrome (PWS) growth hormone therapy (GHT) improves height, body composition, agility and muscular strength. In such patients it is necessary to consider the potential diabetogenic effect of GHT, since they tend to develop type 2 diabetes, particularly after the pubertal age. The aim of our study was to investigate the effects of GHT on glucose and insulin homeostasis in PWS children. An oral glucose tolerance test (OGTT) was performed in 24 prepubertal PWS children (15 male, 9 female, age: 5.8 +/- 2.8 years), 16 were obese (group A) and 8 had normal weight (group B), before and after 2.7 +/- 1.3 years GHT (0.22 +/- 0.03 mg/kg/week) and, only at baseline, in 35 prepubertal children with simple obesity (19 male, 16 female) (group C). Fasting glucose and insulin, glucose tolerance, insulin sensitivity index (ISI), homeostasis model assessment of insulin resistance (HOMA-IR), quick insulin check index (QUICKI), area under the curves (AUC) of glucose and insulin were estimated. At the start of GHT, all PWS children were normoglycaemic and normotolerant but two developed impaired glucose tolerance after 2.2 and 1.9 years of therapy, respectively. At baseline, group A showed lower fasting insulin levels, HOMA-IR and AUC of insulin, higher ISI, QUICKI and AUC of glucose than group C. Comparing groups A and B, AUC of insulin was higher and ISI lower in group A. During GHT, a significant increase of fasting insulin and glucose, a worsening of insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) was found only in group A while ISI did not change. The AUC of glucose decreased in both groups instead AUC of insulin did not change. BMI-SDS decreased in group A and increased in group B. The increased insulin resistance and decreased insulin sensitivity in obese PWS patients, as well as the occurrence of impaired glucose tolerance during GHT, suggest that a close monitoring of glucose and insulin homeostasis is mandatory, especially in treated obese PWS children.     

Development of glucose intolerance and impaired plasma insulin response to glucose in obese hyperglycaemic (ob/ob) mice

The development of glucose intolerance in Aston ob/ob mice showed a gross exaggeration of the age-related changes of glucose tolerance in lean (+/+) mice. Intraperitoneal glucose tolerance in ob/ob mice was poor at 5 weeks, improved by 10 weeks, but markedly worsened by 20 weeks. A 24 hour fast further exaggerated the glucose intolerance of ob/ob mice. Unlike lean mice, tolerance improved in ob/ob mice at 40 weeks. Alterations of insulin sensitivity and the plasma insulin response to glucose accounted in part for these observations. Insulin sensitivity deteriorated until 20 weeks, but improved at 40 weeks in both fed and 24 hour fasted ob/ob mice. A positive plasma insulin response to glucose was lost after 5 weeks in fed ob/ob mice. The severity of this abnormality corresponded with the extent of the basal hyperinsulinaemia. A 24 hour fast reduced plasma insulin concentrations and restored a positive plasma insulin response to glucose in ob/ob mice. The results suggest that the plasma insulin response to glucose in ob/ob mice is related to the secretory activity of the B-cells prior to stimulation. Furthermore, it is evident that factors in addition to insulin insensitivity and the impaired plasma insulin response to glucose contribute to the development of glucose intolerance in these mice.     

Plasma beta-endorphin in response to oral glucose tolerance test in obese patients

In order to clarify the possible interaction between endogenous opioids and glucose homeostasis in obesity we studied Beta-Endorphin (B-Ep), ACTH, cortisol and insulin plasma levels in response to an oral glucose tolerance test (OGTT) in 8 females suffering from uncomplicated obesity and in 6 healthy volunteers of normal weight. Results were evaluated in terms of secretion areas subtracted from basal value. Basal glucose, insulin and B-Ep levels were significantly higher in the obese patients compared to controls, cortisol levels and ACTH were not statistically different between obese and normal subjects. During OGTT total areas of insulin secretion were significantly higher in the obese patients; cortisol, ACTH, B-Ep plasma levels did not change in controls, whereas obese patients showed a response to B-Ep which reached a peak at 60 minutes. The area of B-Ep response to OGTT in obese patients was significantly higher than in controls. On the basis of these results we may suggest that the opioid system belongs to the chain of neuroendocrine and metabolic events responsible for the origin and the growth of overweight. But the possibility exists that obesity itself can enhance the B-Ep secretion above all through overeating. In this regard it is to stress that glucose ingestion induces in obese patients, differently from normal subjects, insulin hypersecretion and the B-Ep secretion, possibly from gastro-enteric tract and/or pancreatic isles.     

Effects of diet composition and fasting on glucose turnover in lean and polygenic obese mice

Effects of high beef tallow (BT), high corn oil (CO) or low-fat (LF) diets upon the outcome of genetic obesity were investigated. Diets were instituted ad libitum at the time of weaning. When mice were six months of age, blood samples were taken 1, 5, 15, 30, and 60 minutes after intravenous injection of glucose-U-¹⁴C. Within dietary treatments, obese and lean mice showed similar plasma glucose-U-¹⁴C disappearance patterns. Plasma glucose disappearance always tended to be faster in ad libitum-fed mice relative to 24-hour fasted mice. Body glucose pool sizes tended to be larger in fed obese BT and LF mice compared to their lean counterparts. This pattern was not seen in non-fasted CO mice. Fasting caused a decrease in body glucose pool sizes in all mice. In contrast to CO and LF mice, lean BT mice appeared to conserve glucose during fasting the same as the obese line. Since the glucose disappearance curves can be described by a two-exponential decay function, at least a two-component or two-pool system must be involved in plasma glucose turnover. Calculated rate constants were used to express interchanges of carbon molecules between the glucose and glycogen pool and the net movement of glucose carbon to a carbon pool representing “irreversible end products”. The data indicate that differences in glucose metabolism, in part, explain the possibility that dietary energy source can overcome the genetic tendency to leanness.     

雷帕霉素对小鼠葡萄糖代谢水平的影响

目的探讨雷帕霉素对葡萄糖代谢水平影响的特点、机制。方法选择4周龄、雄性C57BL/6小鼠,高热量、高脂饮食喂养8周后为肥胖组(HF,n=18),普通饲料喂养为正常组(NC,n=18)。两组小鼠分别给予安慰剂(n=6)、腹腔注射雷帕霉素(2 mg/kg,隔日1次,n=6)、喂饮2.37%亮氨酸水(n=6),2周后分别行灌胃葡萄糖耐量试验(glucose tolerance test,GTT)、胰岛素耐受性试验(insulin tolerance test,ITT)以及胰岛组织病理学检查。结果正常组小鼠腹腔注射雷帕霉素后葡萄糖负荷30min血糖水平显著升高(与安慰剂组比P=0.038,与亮氨酸组比P=0.035)。肥胖组小鼠腹腔注射雷帕霉素后空腹血糖水平显著高于安慰剂组(P=0.031),葡萄糖负荷30 min血糖显著高于安慰剂组(P=0.013)、亮氨酸组(P=0.041)。仅正常组小鼠胰岛素敏感性与安慰剂组相比显著降低(P=0.039)。雷帕霉素干预后腹腔脂肪量显著减少(正常组与安慰剂组比P0.001,肥胖组与安慰剂组比P=0.013)。结论雷帕霉素对哺乳动物糖代谢水平有显著影响,正常小鼠与机体胰岛素敏感性下降有关;肥胖小鼠与胰岛素分泌功能受损、胰岛素抵抗相关。     

Effects of short-term chromium supplementation on insulin sensitivity and body composition in overweight children: randomized, double-blind, placebo-controlled study

Excessive body weight is inversely associated with insulin sensitivity in children and adults. Chromium supplementation produces modest improvement in insulin sensitivity in adults. The aim of this study was to examine the beneficial effects of chromium supplementation on insulin sensitivity and body composition in overweight children simultaneously modifying lifestyle. Twenty-five overweight children aged 9–12 years were randomized to receive either 400 μg of chromium chloride or placebo in double-blind fashion, during a 6-week lifestyle modification regimen that included nutritional education and 3×90 min of aerobic physical activity weekly. Insulin sensitivity was demonstrated using homeostasis model assessment-insulin resistance and quantitative insulin sensitivity check index (QUICKI). Changes in body mass index (BMI; kg/m²), BMI Z-score, waist circumference, body composition and fasting plasma glucose were measured. Although no significant benefit of chromium supplementation over placebo was evident for BMI, BMI Z-score and fasting insulin level, children who received chromium chloride demonstrated more positive changes versus the placebo group in HOMA (−1.84±1.07 vs. 0.05±0.42, P=.05), QUICKI (0.02±0.01 vs. −0.002±0.01, P=.05), lean body mass (2.43±0.68kg vs. 1.36±1.61kg, P=.02) and percentage body fat (−3.32±1.29% vs. 0.65±1.05%, P=.04). The desirable effects of chromium supplementation on insulin sensitivity and body composition were more apparent in pre-pubertal children. These results suggest that short-term chromium supplementation can improve insulin sensitivity and body composition in overweight children.     

Comparison of several insulin sensitivity indices derived from basal plasma insulin and glucose levels with minimal model indices.

Some techniques for the evaluation of insulin resistance (IR), such as the clamp technique, are not viable for the study of large populations; and for this reason, alternative approaches based on fasting plasma glucose (FPG) and plasma insulin (FPI) have been proposed. The aim of this study was to compare the IR calculations obtained from FPI and FPG values with the insulin sensitivity (IS) index derived from the minimal model. Eighty-seven healthy subjects with a wide range of body mass index (18 - 44 kg x m -2) and 16 DM2 non-obese patients were included in the study. All of the patients underwent a frequently sampled intravenous glucose tolerance test (FSIGTT), and the minimal model of glucose was used for the estimation of insulin sensitivity (IS MINIMAL ). The HOMA-IR index, the Avignon index, and the quotient FPG/FPI were used to calculate basal steady-state IR. The basal IR value that best correlated with IS was Log (1/HOMA-IR) (r = 0.70, p < 0.001). All of the basal indices showed a high correlation with each other. In conclusions, insulin sensitivity indices as determined from the basal glycaemia and insulinemia values are not good estimators for metabolic reality from the perspective of the minimal model. Nevertheless, they might well have an IR screening value for epidemiological studies, as long as there is no pancreatic beta-cell dysfunction.     

Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test

The utility of the disposition index as a measure of beta-cell compensatory capacity rests on the established hyperbolic relationship between its component insulin secretion and sensitivity measures as derived from the intravenous glucose tolerance test (IVGTT). If one is to derive an analogous measure of beta-cell compensation from the oral glucose tolerance test (OGTT), it is thus necessary to first establish the existence of this hyperbolic relationship between OGTT-based measures of insulin secretion and insulin sensitivity. In this context, we tested five OGTT-based measures of secretion (insulinogenic index, Stumvoll first phase, Stumvoll second phase, ratio of total area-under-the-insulin-curve to area-under-the-glucose-curve (AUC(ins/gluc)), and incremental AUC(ins/gluc)) with two measures of sensitivity (Matsuda index and 1/Homeostasis Model of Assessment for insulin resistance (HOMA-IR)). Using a model of log(secretion measure) = constant + beta x log(sensitivity measure), a hyperbolic relationship can be established if beta is approximately equal to -1, with 95% confidence interval (CI) excluding 0. In 277 women with normal glucose tolerance (NGT), the pairing of total AUC(ins/gluc) and Matsuda index was the only combination that satisfied these criteria (beta = -0.99, 95% CI (-1.66, -0.33)). This pairing also satisfied hyperbolic criteria in 53 women with impaired glucose tolerance (IGT) (beta = -1.02, (-1.72, -0.32)). In a separate data set, this pairing yielded distinct hyperbolae for NGT (n = 245) (beta = -0.99, (-1.67, -0.32)), IGT (n = 116) (beta = -1.18, (-1.84, -0.53)), and diabetes (n = 43) (beta = -1.37, (-2.46, -0.29)). Moreover, the product of AUC(ins/gluc) and Matsuda index progressively decreased from NGT (212) to IGT (193) to diabetes (104) (P < 0.001), consistent with declining beta-cell function. In summary, a hyperbolic relationship can be demonstrated between OGTT-derived AUC(ins/gluc) and Matsuda index across a range of glucose tolerance. Based on these findings, the product of these two indices emerges as a potential OGTT-based measure of beta-cell function.     

Effects of cholinergic stimulation and antagonism on plasma insulin concentration in lean and obese human subjects

The effect of cholinomimetic stimulation by infusion of edrophonium chloride or muscarinic blockade by infusion of atropine sulfate on insulin and GIP secretion was studied in normal lean subjects during eu- and hyperglycemia. Cholinomimetic stimulation led to a slight non-significant increase and muscarinic blockade to a slight, non-significant suppression of both GIP and insulin. No modification of the insulin secretion pattern was observed under either condition during hyperglycemia. The effect of atropine infusion on fasting plasma insulin and GIP was subsequently studied in 11 obese patients and 10 lean subjects. Muscarinic antagonism by atropine led to a transient non-significant suppression of GIP and insulin in lean subjects, but to a significant, sustained suppression of these hormones in obese patients. Insulin and GIP levels were however, not suppressed to control values after atropine administration in obese patients. A positive correlation was found between fasting plasma insulin and maximal suppression of insulin attained during the 30 min following administration of atropine. It is concluded that part of the hyperinsulinemia observed in human obesity is under the control of the parasympathetic nervous system. An abnormal balance between sympathetic inhibitory and parasympathetic stimulatory tones on insulin secretion, as observed in the VMH lesioned rat, might be present in human obesity.