Caloric restriction recovers impaired beta-cell-beta-cell gap junction coupling, calcium oscillation coordination, and insulin secretion in prediabetic mice

Author(s)

Corezola da Amaral, Maria Esmeria ^[1] ; Kravets, Vira ^{[2, 3]} ; Dwulet, JaeAnn M. ^[3] ; Farnsworth, Nikki L. ^[2] ; Piscopio, Robert ^[3] ; Schleicher, Wolfgang E. ^[3] ; Miranda, Jose Guadalupe ^[3] ; Benninger, Richard K. P. ^{[2, 3]}

Affiliation

^[1] Ctr Univ Fundacao Herminio Ometto, Grad Program Biomed Sci, Araras, SP - Brazil

^[2] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Anschutz Med Campus, Denver, CO 80045 - USA

^[3] Univ Colorado, Dept Bioengn, Anschutz Med Campus, Denver, CO 80045 - USA

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM; v. 319, n. 4, p. E709-E720, OCT 2020.
• Web of Science Citations: 5

Abstract

Caloric restriction can decrease the incidence of metabolic diseases, such as obesity and Type 2 diabetes mellitus. The mechanisms underlying the benefits of caloric restriction involved in insulin secretion and glucose homeostasis are not fully understood. Intercellular communication within the islets of Langerhans, mediated by Connexin36 (Cx36) gap junctions, regulates insulin secretion dynamics and glucose homeostasis. The goal of this study was to determine whether caloric restriction can protect against decreases in Cx36 gap junction coupling and altered islet function induced in models of obesity and prediabetes. C57BL6 mice were fed with a high-fat diet (HFD), showing indications of prediabetes after 2 mo, including weight gain, insulin resistance, and elevated fasting glucose and insulin levels. Subsequently, mice were submitted to 1 mo of 40% caloric restriction (2 g/day of HFD). Mice under 40% caloric restriction showed reversal in weight gain and recovered insulin sensitivity, fasting glucose, and insulin levels. In islets of mice fed the HFD, caloric restriction protected against obesity-induced decreases in gap junction coupling and preserved glucose-stimulated calcium signaling, including Ca2+ oscillation coordination and oscillation amplitude. Caloric restriction also promoted a slight increase in glucose metabolism, as measured by increased NAD(P)H autofluorescence, as well as recovering glucose-stimulated insulin secretion. We conclude that declines in Cx36 gap junction coupling that occur in obesity can be completely recovered by caloric restriction and obesity reversal, improving Ca2+ dynamics and insulin secretion regulation. This suggests a critical role for caloric restriction in the context of obesity to prevent islet dysfunction. (AU)

• FAPESP's process: 18/04536-6 - Effect of caloric restriction on isolated pancreatic islets on cell coupling, impact of electrical activity and intracellular Ca 2+ oscillation
• Grantee: Maria Esméria Corezola do Amaral
• Support Opportunities: Scholarships abroad - Research