Molecular mechanisms of diabetes reversibility after bariatric surgery

Rosa, G. De; Mingrone, Geltrude; Manco, Melania; Euthine, Vanessa; Gniuli, Donatella; Calvani, Riccardo; Calvani, Menotti; Favuzzi, Angela Maria Rita; Castagneto, Marco; Vidal, Hubert

doi:10.1038/sj.ijo.0803630

Cited by 20 publications

(7 citation statements)

References 50 publications

(46 reference statements)

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“…27,50,51,93,94,96,112,113,128–138 The results from these studies demonstrate that skeletal muscle insulin sensitivity does not change after moderate (~10%) weight loss, 2–4 weeks after RYGB surgery, 50,51 but increases markedly after greater (20%–40%) weight loss, 6–16 months after surgery. 50,128–132,134,137 A similar improvement in insulin sensitivity (~150%) has been reported after marked weight loss (~33%) induced by vertical banded gastroplasty. 136 In addition, we have found that 20% weight loss induced by either LAGB or RYGB causes nearly a two-fold increase in skeletal muscle insulin sensitivity, assessed by using the HEC procedure in conjunction with stable isotopically-labeled tracer infusion, but there was no difference between the two surgical groups.…”

Section: Effect Of Bariatric Surgery On Insulin Sensitivitysupporting

confidence: 69%

Effects of Bariatric Surgery on Glucose Homeostasis and Type 2 Diabetes

2012

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Obesity is an important risk factor for type 2 diabetes (T2D). Weight loss improves the major factors involved in the pathogenesis of T2D, namely insulin action and β-cell function, and is considered a primary therapy for obese patients who have T2D. Unfortunately, most patients with T2D fail to achieve successful weight loss and adequate glycemic control from medical therapy. In contrast, bariatric surgery causes marked weight loss and complete remission of T2D in most patients. Moreover, bariatric surgical procedures that divert nutrients away from the upper gastrointestinal tract are more successful in producing weight loss and remission of T2D than those that simply restrict stomach capacity. Although upper gastrointestinal tract bypass procedures alter the metabolic response to meal ingestion, by increasing early post-prandial plasma concentrations of glucagon-like peptide 1 and insulin, it is not clear whether these effects make an important contribution to long-term control of glycemia and T2D once substantial surgery-induced weight loss has occurred. Nonetheless, the effects of surgery on body weight and metabolic function indicate that bariatric surgery should be part of the standard therapy for T2D. More research is needed to advance our understanding of the physiological effects of different bariatric surgical procedures and possible weight loss-independent factors that improve metabolic function and contribute to the resolution of T2D.

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Section: Effect Of Bariatric Surgery On Insulin Sensitivitysupporting

confidence: 69%

Effects of Bariatric Surgery on Glucose Homeostasis and Type 2 Diabetes

2012

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“…In these studies, HOMA and glucose disposal improved significantly [ 35 – 38 ]. The improvement we see at 1mU/kg/min is of similar magnitude to that reported in other studies [ 37 ], however our study is the first to undertake a detailed examination across a range of plasma insulin concentrations.…”

Section: Discussionsupporting

confidence: 89%

Bariatric Surgery in Morbidly Obese Insulin Resistant Humans Normalises Insulin Signalling but Not Insulin-Stimulated Glucose Disposal

et al. 2015

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AimsWeight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB), and compared this to lean volunteers.Materials and MethodsThe hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR) in eight morbidly obese (body mass index, BMI=47.3±2.2 kg/m2) patients, before and after RYGB, and in eight lean volunteers (BMI=20.7±0.7 kg/m2). Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50) and maximal (GDR100) GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity.ResultsPre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001). Weight-loss of 29.9±4 kg after surgery significantly improved GDR50 (P=0.004) but not GDR100 (P=0.3). These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001). Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA), and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA), and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively).ConclusionsOur data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.

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“…Consistent with this hypothesis is the fact that bilio-pancreatic diversion (BPD), an operation that involves the greatest length of intestinal bypass (the duodenum and jejunum in their entirety) is associated with the best rates of long-term remission of diabetes (5,12). BPD results in major improvement of skeletal muscle S I , mediated by changes in the expression of genes that regulate glucose and fatty acid metabolism in response to nutrient availability (43).…”

Section: Discussionmentioning

confidence: 78%

Duodenal-Jejunal Bypass and Jejunectomy Improve Insulin Sensitivity in Goto-Kakizaki Diabetic Rats Without Changes in Incretins or Insulin Secretion

et al. 2014

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Gastric bypass surgery can dramatically improve type 2 diabetes. It has been hypothesized that by excluding duodenum and jejunum from nutrient transit, this procedure may reduce putative signals from the proximal intestine that negatively influence insulin sensitivity (SI). To test this hypothesis, resection or bypass of different intestinal segments were performed in diabetic Goto-Kakizaki and Wistar rats. Rats were randomly assigned to five groups: duodenal-jejunal bypass (DJB), jejunal resection (jejunectomy), ileal resection (ileectomy), pair-fed sham-operated, and nonoperated controls. Oral glucose tolerance test was performed within 2 weeks after surgery. Baseline and poststimulation levels of glucose, insulin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured. Minimal model analysis was used to assess SI. SI improved after DJB (SI = 1.14 ± 0.32 × 10(-4) min(-1) ⋅ pM(-1)) and jejunectomy (SI = 0.80 ± 0.14 × 10(-4) min(-1) ⋅ pM(-1)), but not after ileectomy or sham operation/pair feeding in diabetic rats. Both DJB and jejunal resection normalized SI in diabetic rats as shown by SI levels equivalent to those of Wistar rats (SI = 1.01 ± 0.06 × 10(-4) min(-1) ⋅ pM(-1); P = NS). Glucose effectiveness did not change after operations in any group. While ileectomy increased plasma GIP levels, no changes in GIP or GLP-1 were observed after DJB and jejunectomy. These findings support the hypothesis that anatomic alterations of the proximal small bowel may reduce factors associated with negative influence on SI, therefore contributing to the control of diabetes after gastric bypass surgery

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Molecular mechanisms of diabetes reversibility after bariatric surgery

Cited by 20 publications

References 50 publications

Effects of Bariatric Surgery on Glucose Homeostasis and Type 2 Diabetes

Effects of Bariatric Surgery on Glucose Homeostasis and Type 2 Diabetes

Bariatric Surgery in Morbidly Obese Insulin Resistant Humans Normalises Insulin Signalling but Not Insulin-Stimulated Glucose Disposal

Duodenal-Jejunal Bypass and Jejunectomy Improve Insulin Sensitivity in Goto-Kakizaki Diabetic Rats Without Changes in Incretins or Insulin Secretion

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