Glucagon-Producing Cell Expansion in Wistar Rats. Changes to Islet Architecture After Sleeve Gastrectomy

Abstract

Purpose Many studies about bariatric surgery have analyzed the effect of sleeve gastrectomy (SG) on glucose improvement, beta-cell mass, and islet size modification. The effects of SG on the other endocrine cells of the pancreas, such as the alpha-cell population, and their regulatory mechanisms remain less studied. Materials and Methods We focused our work on the changes in the alpha-cell population after SG in a healthy model of Wistar rats. We measured alpha-cell mass, glucose tolerance, and insulin release after oral glucose tolerance tests and plasma glucagon secretion patterns after insulin infusion. Three Wistar rat groups were employed: SG-operated, surgical control (Sham), and fasting control. Results The results obtained showed significant increases in the alpha-cell population after SG. The result was an increase in beta-cell transdifferentiation; it was shown by some expressed molecules (the loss of expression of Pdx-1 and the increase in Arx and Pax6 cells/mm2 of islet). The serum results were enhanced plasma glucagon secretion pattern after insulin infusion assays and normal glucose tolerance and insulin release after OGTT. Conclusion We concluded that SG leads to an expansion of the alpha-cell population, at expense of beta-cell; this expansion of alpha-cells is related to transdifferentiation. Plasma glucose level was not affected due to an increased glucagon response.

Combined Sleeve Gastrectomy and Omentoplasty Improves Inflammation and Insulin Resistance in Obese Rats with Type II Diabetes Mellitus: A Randomized Controlled Trials

“…(28) Another research indicated that SG combined with pancreatic omentoplasty significantly reduces IL-1 levels and increases pancreatic β cell expression in rats with T2DM. (29) The decrease in IL-10 levels found in all three groups is consistent with previous studies stating that levels of anti-inflammatory cytokines, including IL-10, decrease in morbidly obese patients with sleep apnea. (31) IL-10 is known to inhibit inflammation by increasing immune responses during inflammatory events.…”

“…(27) Furthermore, based on another study on rats, SG was found to expand the alpha-cell population at the expense of betacells, contributing to increased glucagon response without affecting plasma glucose levels. (29) Obesity's surplus adipose tissue influences metabolism by releasing hormones, glycerol, and various substances like leptin, cytokines, adiponectin, and pro-inflammatory agents, as well as by liberating Non-esterified fatty acids (NEFA). The rise in HOMA-IR levels among the control group indicates insulin resistance induced by obesity and DM.…”

The role of glucagon after bariatric/metabolic surgery: much more than an “anti-insulin” hormone

“…Elevated glucagon: insulin ratios have been reported in diabetic-GK rats after SG, and an early increase in serum glucagon levels has been reported in patients. These findings are consistent with what was observed in previous studies by our group reporting a long-term increase in pancreatic alpha cell mass in healthy rodents after SG with potent glucagon secretion capable of buffering exogenous insulin administration ( 56 ). This finding could explain the improved insulin secretion reported after SG because beta cell-expressing GCGR is activated by glucagon in rodents.…”

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

“…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 ). Moreover, this is supported by studies performed on mice outside the scope of bariatric surgery where alpha-cell populations labeled with Gcg-Cre lineage tracers showed a dilution of the marker at the expense of the beta-cell population throughout life [ 26 ].…”

“…In this sense, RYGB is also able to cause an increase in the alpha-cell population in mice six months after the operation, including a loss of beta identity markers such as PDX-1 and a gain of alpha-cell markers such as ARX in the islets ( Figure 2 ). All of this suggests long-term trans-differentiation of beta-cells into alpha-cells after surgery [ 25 ].…”