No effect of inhibition of insulin secretion by diazoxide on weight loss in hyperinsulinaemic obese subjects during an 8‐week weight‐loss diet

Due, Anette Pia; Flint, Anne; Eriksen, Gunnar Sundstøl; Møller, Bente K.; Raben, Anne; Hansen, John Bondo; Astrup, Arne

doi:10.1111/j.1463-1326.2006.00645.x

Cited by 23 publications

(27 citation statements)

References 22 publications

(35 reference statements)

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“…The reduction of body weight and fat is known to improve peripheral insulin resistance, but few studies have been carried out to investigate the nature of glucose-stimulated insulin secretion and β-cell mass (Manco and Mingrone, 2005). Our previous study, among others conducted on this topic, revealed that diet-induced weight loss did not modulate glucose-stimulated insulin secretion and β-cell proliferation (Choi et al, 2005;Due et al, 2007;Manco and Mingrone, 2005). These results support the contention that the insulinotropic action of exendin-4 and exercise had independent effects unrelated to other factors.…”

Section: Discussionmentioning

confidence: 97%

Exendin-4 and exercise promotes β-cell function and mass through IRS2 induction in islets of diabetic rats

2008

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Section: Discussionmentioning

confidence: 97%

Exendin-4 and exercise promotes β-cell function and mass through IRS2 induction in islets of diabetic rats

2008

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“…At the clinical level, a few studies have been conducted in obese subjects using diazoxide to inhibit insulin secretion from the ␤-cell. Short term treatments showed contradictory results with either no change in body weight (45) or anti-obesity effect in hyperinsulinemic obese adults (46). A 6-month diazoxide treatment of obese hyperinsulinemic men, combined with moderate caloric restriction, resulted in lower fasting insulin levels associated with significant weight loss, in particular of the fat mass (23).…”

Section: Discussionmentioning

confidence: 99%

The Amplifying Pathway of the β-Cell Contributes to Diet-induced Obesity

Vetterli¹,

Carobbio²,

Frigerio³

et al. 2016

Journal of Biological Chemistry

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Efficient energy storage in adipose tissues requires optimal function of the insulin-producing ␤-cell, whereas its dysfunction promotes diabetes. The associated paradox related to ␤-cell efficiency is that excessive accumulation of fat in adipose tissue predisposes for type 2 diabetes. Insulin exocytosis is regulated by intracellular metabolic signal transduction, with glutamate dehydrogenase playing a key role in the amplification of the secretory response. Here, we used mice with ␤-cell-selective glutamate dehydrogenase deletion (␤Glud1 ؊/؊ ), lacking an amplifying pathway of insulin secretion. As opposed to control mice, ␤Glud1 ؊/؊ animals fed a high calorie diet maintained glucose tolerance and did not develop diet-induced obesity. Islets of ␤Glud1 ؊/؊ mice did not increase their secretory response upon high calorie feeding, as did islets of control mice. Inhibited adipose tissue expansion observed in knock-out mice correlated with lower expression of genes responsible for adipogenesis. Rather than being efficiently stored, lipids were consumed at a higher rate in ␤Glud1 ؊/؊ mice compared with controls, in particular during food intake periods. These results show that reduced ␤-cell function prior to high calorie feeding prevented diet-induced obesity.

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“…Although there was no improvement in glucose tolerance observed compared to that in placebo, there were also no adverse effects despite a large reduction in postprandial insulin secretion. In contrast, a second trial with a similar design did not observe any significant additional weight loss with diazoxide supplementation [82]. The basis for the discrepancies between these two trials is currently unclear.…”

Section: Effect Of Reducing Himentioning

confidence: 99%

Hyperinsulinemia: a Cause of Obesity?

2017

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Purpose of ReviewThis perspective is motivated by the need to question dogma that does not work: that the problem is insulin resistance (IR). We highlight the need to investigate potential environmental obesogens and toxins.Recent FindingsThe prequel to severe metabolic disease includes three interacting components that are abnormal: (a) IR, (b) elevated lipids and (c) elevated basal insulin (HI). HI is more common than IR and is a significant independent predictor of diabetes.SummaryWe hypothesize that (1) the initiating defect is HI that increases nutrient consumption and hyperlipidemia (HL); (2) the cause of HI may include food additives, environmental obesogens or toxins that have entered our food supply since 1980; and (3) HI is sustained by HL derived from increased adipose mass and leads to IR. We suggest that HI and HL are early indicators of metabolic dysfunction and treating and reversing these abnormalities may prevent the development of more serious metabolic disease.

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No effect of inhibition of insulin secretion by diazoxide on weight loss in hyperinsulinaemic obese subjects during an 8‐week weight‐loss diet

Abstract: These findings do not suggest that hyperinsulinaemia per se contributes to maintenance of the obese state, and insulin secretion inhibition seems not a promising drug target.

Cited by 23 publications

References 22 publications

Exendin-4 and exercise promotes β-cell function and mass through IRS2 induction in islets of diabetic rats

Exendin-4 and exercise promotes β-cell function and mass through IRS2 induction in islets of diabetic rats

The Amplifying Pathway of the β-Cell Contributes to Diet-induced Obesity

Hyperinsulinemia: a Cause of Obesity?

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