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      β-Cell Control of Insulin Production During Starvation-Refeeding in Male Rats

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          Abstract

          Mammalian metabolism has evolved to adapt to changes in nutrient status. Insulin, the key anabolic hormone, facilitates intracellular storage of nutrient fuels and plays a pivotal role in the transition away from catabolism upon refeeding. Although circulating insulin relative to nutrient levels has been well characterized during fasting and refeeding, how pancreatic β-cell biology caters to acute changes in insulin demand has not been sufficiently addressed. Here, we examined the dynamics of (pro)insulin production and associated changes in β-cell ultrastructure during refeeding after a 72-hour fast in male rats. We found that fasted β-cells had marked degranulation, which inversely coordinated with the upregulation of autophagolysomal and lysosomal organelles. There was also expanded Golgi that correlated with enhanced (pro)insulin biosynthetic capacity but, conversely, blunted in vivo insulin secretion. Within 4 to 6 hours of refeeding, proinsulin biosynthesis, cellular ultrastructure, in vivo insulin secretion, and glucose tolerance normalized to levels near those of fed control animals, indicating a rapid replenishment of normal insulin secretory capacity. Thus, during a prolonged fast, the β-cell protects against hypoglycemia by markedly reducing insulin secretory capacity in vivo but is simultaneously poised to efficiently increase (pro)insulin production upon refeeding to effectively return normal insulin secretory capacity within hours.

          Abstract

          Rapid β-cell ultrastructural changes parallel increased (pro)insulin biosynthesis to meet glycemic demand after fasting-refeeding in rats.

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          Author and article information

          Journal
          Endocrinology
          Endocrinology
          endo
          endo
          Endocrinology
          Endocrine Society (Washington, DC )
          0013-7227
          1945-7170
          13 December 2017
          February 2018
          : 159
          : 2
          : 895-906
          Affiliations
          [1 ]Kovler Diabetes Center, Department of Medicine Section of Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, Illinois 60637
          [2 ]Division of Cardiovascular and Metabolic Disease, MedImmune LLC, Gaithersburg, Maryland 20878
          Author notes
          Correspondence:  Brandon B. Boland, PhD, MedImmune, LLC, 1 MedImmune Way, Gaithersburg, Maryland 20878. E-mail: bolandb@ 123456medimmune.com .
          Article
          PMC5776497 PMC5776497 5776497 endo_201703120
          10.1210/en.2017-03120
          5776497
          29244064
          Copyright © 2018 Endocrine Society
          Page count
          Figures: 6, Tables: 0, Equations: 0, References: 43, Pages: 12
          Categories
          Research Articles
          Diabetes, Pancreatic and Gastrointestinal Hormones

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