Diabetes recurrence after metabolic surgeries correlates with re-impaired insulin sensitivity rather than beta-cell function

Abstract

AIMTo investigate factors causing diabetes recurrence after sleeve gastrectomy (SG) and duodenal-jejunal bypass (DJB).METHODSSG and DJB were performed on rats with diabetes induced by high-fat diet (HFD) and streptozotocin (STZ). HFD was used to induce diabetes recurrence at 4 wk postoperatively. Body weight, oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR), insulin signaling [IR, insulin receptor substrate (IRS)1, IRS2, phosphatidylinositol 3-kinase and AKT in liver and skeletal muscle], oral glucose stimulated insulin secretion, beta-cell morphology (mass, apoptosis and insulin secretion), glucagon-like peptide (GLP)-1, PYY and ghrelin were compared among SG rats with common low-fat diet (SG-LFD), SG with HFD (SG-HFD), DJB rats with LFD (DJB-LFD), DJB with HFD (DJB-HFD) and sham-operation with LFD (Sham) at targeted postoperative times.RESULTSSG and DJB resulted in significant improvement in glucose tolerance, lower HOMA-IR, up-regulated hepatic and muscular insulin signaling, higher levels of oral glucose-stimulated insulin secretion, bigger beta-cell mass, higher immunofluorescence intensity of insulin, fewer transferase-mediated dUTP-biotin 3’ nick end-labeling (TUNEL)-positive beta cells and higher postprandial GLP-1 and PYY levels than in the Sham group. The improvement in glucose tolerance was reversed at 12 wk postoperatively. Compared with the SG-LFD and DJB-LFD groups, the SG-HFD and DJB-HFD groups showed higher HOMA-IR, down-regulated hepatic and muscular insulin signaling, and more TUNEL-positive beta cells. No significant difference was detected between HFD and LFD groups for body weight, glucose-stimulated insulin secretion, beta-cell mass, immunofluorescence intensity of insulin, and postprandial GLP-1 and PYY levels. Fasting serum ghrelin decreased in SG groups, and there was no difference between HFD-SG and LFD-SG groups.CONCLUSIONHFD reverses the improvement in glucose homeostasis after SG and DJB. Diabetes recurrence may correlate with re-impaired insulin sensitivity, but not with alterations of beta-cell function and body weight.

Sleeve Gastrectomy Improves Hepatic Glucose Metabolism by Downregulating FBXO2 and Activating the PI3K-AKT Pathway

“…One possible explanation is that the destruction of substrate IRS1/2 will cause insulin resistance. In addition, many studies have shown that the level of IRS1/2 increases after bariatric surgery [ 35 , 36 ]. These studies provide important insight into the mechanism of PI3K-AKT pathway activation after weight-loss surgery.…”

Preoperative predictors of early relapse/no‐remission of type‐2 diabetes after metabolic surgery in Chinese patients

“…At present the physiological and molecular mechanisms underlying diabetes remission and relapse after metabolic surgery remains incompletely understood, although in the early stage diabetes remission is mainly due to improvement in insulin sensitivity . Recently Lui Teng based on animal model study found that rapidly improved insulin sensitivity after metabolic surgery relapsed after 8 weeks of high calorie, high‐fat diet (HFD) gavage. They concluded that relapse of hepatic and muscular insulin sensitivity due to HFD is likely responsible for the relapse, not alterations of beta‐cell function and weight regain.…”

Sleeve Gastrectomy and Roux-En-Y Gastric Bypass. Two Sculptors of the Pancreatic Islet

“…This brings us to the problem of diabetes relapse after SG, which is as high as 41.6% of cases five years after surgery [ 2 ]. Liu et al proposed long-term recovery of insulin sensitivity without beta-cell dysfunction as an answer to the question [ 24 ], but a recent work showed loss of beta-cell mass and a strong increase in alpha-cell mass in Wistar rats twelve weeks after SG. Trans-differentiation of the beta-cell population under stressful situations with loss of beta-cell markers such as PDX-1 and gain of alpha-cell markers such as Pax-6 and Arx has been shown [ 25 ] ( Figure 2 ).…”