Lack of insulin inhibition on insulin secretion in non-diabetic morbidly obese patients

Muscelli, Elza; Pereira, Juliana Vianna; Lazarin, Mact; Silva, CA da; Pareja, José Francisco Pascual; Saad, Mário J.A.

doi:10.1038/sj.ijo.0801607

Cited by 9 publications

(11 citation statements)

References 47 publications

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“…30,31 In a previous study, insulin infusion under euglycemic conditions at steady state inhibited its own secretion in lean subjects but this insulin action was blunted in the obese group. 7 In this study we observed that in severely obese patients insulin-induced inhibition of insulin secretion was blunted before surgery (SI) compared to the control group, suggesting insulin resistance to this effect. After weight loss, the decrease in C-peptide during insulin infusion improved.…”

Section: Discussionmentioning

confidence: 72%

“…In a previous study, we observed a failure of insulin feedback on insulin secretion in extreme obesity (BMI440 kg/m 2 ), while in lean subjects the insulin inhibition was directly related to insulin sensitivity. 7 Since severe obesity (obese class III 13 ) usually displays serious metabolic alterations 13,14 that can be changed by weight loss, [14][15][16][17] and the effect of weight loss on the insulin inhibition on insulin secretion was not yet investigated, the present study was designed to examine the impact of experimentally induced hyperinsulinemia under euglycemic conditions on its own secretion in these patients, before and after surgically (vertical banded gastroplastyFgastric bypassFCapella technique) induced weight loss. 18,19 C-peptide, which is the connecting peptide of proinsulin, is secreted from b cells in equimolar amounts with insulin, and its concentrations have been used to determine insulin production in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…6 Insulin levels are a result of the rate of insulin secretion and of its metabolic clearance rate. In obese individuals, the posthepatic metabolic clearance rate is thought to be normal 7 and insulin secretion is enhanced. 3,8 Insulin secretion is, in turn, determined by complex stimulatory and inhibitory influences on the b cell.…”

Section: Introductionmentioning

confidence: 99%

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Restored insulin inhibition on insulin secretion in nondiabetic severely obese patients after weight loss induced by bariatric surgery

et al. 2003

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OBJECTIVE:To examine the impact of important weight loss on insulin inhibition of its own secretion during experimentally induced hyperinsulinemia under euglycemic conditions. DESIGN: Longitudinal, clinical intervention studyFbariatric surgery (vertical banded gastroplastyFgastric bypassFCapella technique), re-evaluation after 4 and 14 months. SUBJECTS: Nine obese patients class III (BMI ¼ 54.672.6 kg/m 2 ) and nine lean subjects (BMI ¼ 22.770.7 kg/m 2 ). MEASUREMENTS: Euglycemic hyperinsulinemic clamp (insulin infusion: 40 mU/min m 2 ), C-peptide plasma levels, electrical bioimpedance methodology, and oral glucose tolerance test (OGTT). RESULTS: BMI was reduced in the follow-up: 44.572.2 and 33.971.5 kg/m 2 at 4 and 14 months. Insulin-induced glucose uptake was markedly reduced in obese patients (19.571.9 mmol/min kg FFM) and improved with weight loss, but in the third study, it was still lower than that observed in controls (35.974.0 vs 52.972.2 mmol/min kg FFM). Insulin-induced inhibition of its own secretion was blunted in obese patients (19.975.7%, relative to fasting values), and completely reversed to values similar to that of lean ones in the second and third studies (À60.874.2 and À54.076.1%, respectively). CONCLUSION: Weight loss in severe obesity improved insulin-induced glucose uptake, and completely normalized the insulin inhibition on its own secretion.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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Restored insulin inhibition on insulin secretion in nondiabetic severely obese patients after weight loss induced by bariatric surgery

et al. 2003

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“…Interestingly, it has previously been shown that insulin inhibition of insulin secretion during HEC, as measured by the decrease in C-peptide levels, is correlated with IS (19). Tracer dilution during HEC further makes it possible to assess the ability of insulin to suppress EGR.…”

Section: Rdnmentioning

confidence: 99%

Renal Denervation for Resistant Hypertension Fails to Improve Insulin Resistance as Assessed by Hyperinsulinemic-Euglycemic Step Clamp

et al. 2016

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We assessed whether insulin sensitivity improved after renal denervation (RDN) for resistant hypertension. Twentythree patients underwent a two-step hyperinsulinemiceuglycemic clamp (HEC) with glucose tracer and labeled glucose infusion and oral glucose tolerance test (OGTT) before and 6 months after RDN. Eighteen patients had metabolic syndrome at baseline. Blood pressure declined significantly after RDN, whereas mean (SD) fasting plasma glucose concentration (5.9 6 0.7 mmol/L), median (minimum-maximum) insulin concentration (254 pmol/L [88-797 pmol/L]), and median C-peptide concentration (2.4 nmol/L [0.9-5.7 nmol/L]) remained unchanged. Endogenous glucose release during HEC was less suppressed after RDN, suggesting a slight decrease in hepatic insulin sensitivity. During high-dose insulin infusion, whole-body glucose disposal was low and remained unchanged after RDN, indicating persistent peripheral insulin resistance (IR). Area under the curve for 0-120 min for glucose and insulin during OGTT, Quantitative Insulin Sensitivity Check Index, Simple Index Assessing Insulin Sensitivity Oral Glucose Tolerance, and HOMA-IR were high, and did not improve after RDN. Despite a significant decrease in blood pressure, neither peripheral nor hepatic insulin sensitivity improved 6 months after RDN treatment in this group of insulin-resistant patients without diabetes and with resistant hypertension, as measured with gold standard methods.More than 50% of patients with essential hypertension are considered to have insulin resistance (IR) (1). The link between these two disorders is partly unknown, but it has been hypothesized that increased sympathetic nerve activity (SNA) plays an important role (2). Sympathetic activation results in peripheral vasoconstriction through the release of norepinephrine, which acts upon vascular muscle adrenoreceptors. A subsequent reduction in skeletal muscle blood flow leads to reduced whole-body glucose utilization (3). Consequently, increased SNA may reduce insulin sensitivity (IS) through direct effects on the regulation of glucose uptake by skeletal muscle (4,5).Targeting both sympathetic tone and IR might be of relevance to reduce the cardiovascular risk associated with hypertension. Renal denervation (RDN) has been shown to lower SNA by the ablation of both afferent and efferent nerves (6). The first study showing improved IS after RDN used only surrogate indexes of whole-body IR (7). To investigate the possible effects of RDN on IR in more detail, we applied a two-step hyperinsulinemiceuglycemic clamp (HEC) with glucose tracer infusion and labeled glucose infusate to separately assess glucose turnover, as well as hepatic and peripheral IS before and after RDN. Patients were also subjected to an oral glucose tolerance test (OGTT).

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“…1). In support of this suggestion, it has been shown that despite increased resting SNS tone, obesity is characterised by a blunted responsiveness to sympathetic stimuli, such as insulin (examined during a meal or during a hyperinsulinaemic-euglycaemic clamp) [4,26]. In a study by Muscelli et al, although the basal (resting) low frequency (LF)/high frequency (HF) ratio (a HRV measure of sympathovagal balance) was higher in obese vs lean individuals, insulin failed to increase the LF/HF ratio in obese subjects [27].…”

Section: Is Obesity Characterised By Altered Sns Ac-tivity?mentioning

confidence: 94%

Role of the Autonomic Nervous System and Neuropeptides in the Development of Obesity in Humans: Targets for Therapy?

Greenfield

Campbell²

2008

CPD

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Obesity and type 2 diabetes have reached epidemic proportions worldwide. These metabolic disorders, particularly obesity, are characterised by increased basal sympathetic nervous system (SNS) activity but an impaired sympathetic response to certain stimuli, such as insulin. Although targeting the SNS may seem an attractive avenue for the pharmacological prevention and treatment of obesity and related metabolic disorders, it remains unknown whether changes in SNS tone are primary and contribute to the development of these metabolic conditions or whether they develop secondary to the obese state. This question can be answered by the study of insulin-resistant individuals prior to the development of obesity and type 2 diabetes. Using this model, it has been shown that early insulin resistance is associated with increased SNS activity in genetically-predisposed humans. It has been suggested that in insulin-resistant states, hyperinsulinaemia is the initiating factor that increases sympathetic neural activity. Over time, adrenoreceptor down-regulation and/or reduced sensitivity are likely to develop, resulting in reduced sympathetic responsiveness. In the postprandial state, this will lead to impaired diet-induced thermogenesis and post-prandial fat oxidation, promoting the accumulation of body fat. More recent evidence demonstrates that stress-induced SNS overactivity up-regulates Neuropeptide Y, an orexigenic hormone, and its Y2 receptor, in visceral adipose tissue, the fat depot most strongly linked to insulin resistance and type 2 diabetes. There is evidence that SNS overactivity specifically contributes to the development of abdominal obesity via this pathway, which could represent a novel target for the prevention and treatment of abdominal obesity and related metabolic consequences.

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Lack of insulin inhibition on insulin secretion in non-diabetic morbidly obese patients

Cited by 9 publications

References 47 publications

Restored insulin inhibition on insulin secretion in nondiabetic severely obese patients after weight loss induced by bariatric surgery

Restored insulin inhibition on insulin secretion in nondiabetic severely obese patients after weight loss induced by bariatric surgery

Renal Denervation for Resistant Hypertension Fails to Improve Insulin Resistance as Assessed by Hyperinsulinemic-Euglycemic Step Clamp

Role of the Autonomic Nervous System and Neuropeptides in the Development of Obesity in Humans: Targets for Therapy?

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