Kisspeptin-Activated Autophagy Independently Suppresses Non-Glucose-Stimulated Insulin Secretion from Pancreatic β-Cells
Journal
Scientific reports
Journal Volume
9
Journal Issue
1
Date Issued
2019
Author(s)
Wang, Hao-Yi
Wang, Mu-En
Wu, Yi-Hsieng Samuel
Abstract
Previous studies have demonstrated the important role of kisspeptin in impaired glucose-stimulated insulin secretion (GSIS). In addition, it was reported that the activation of autophagy in pancreatic β-cells decreases insulin secretion by selectively degrading insulin granules. However, it is currently unknown whether kisspeptin suppresses GSIS in β-cells by activating autophagy. To investigate the involvement of autophagy in kisspeptin-regulated insulin secretion, we overexpressed Kiss1 in NIT-1 cells to mimic the long-term exposure of pancreatic β-cells to kisspeptin during type 2 diabetes (T2D). Interestingly, our data showed that although kisspeptin potently decreases the intracellular proinsulin and insulin ((pro)insulin) content and insulin secretion of NIT-1 cells, autophagy inhibition using bafilomycin A1 and Atg5 siRNAs only rescues basal insulin secretion, not kisspeptin-impaired GSIS. We also generated a novel in vivo model to investigate the long-term exposure of kisspeptin by osmotic pump. The in vivo data demonstrated that kisspeptin lowers GSIS and (pro)insulin levels and also activated pancreatic autophagy in mice. Collectively, our data demonstrated that kisspeptin suppresses both GSIS and non-glucose-stimulated insulin secretion of pancreatic β-cells, but only non-glucose-stimulated insulin secretion depends on activated autophagic degradation of (pro)insulin. Our study provides novel insights for the development of impaired insulin secretion during T2D progression.
SDGs
Other Subjects
glucose; insulin; Kiss1 protein, mouse; kisspeptin; proinsulin; recombinant protein; animal; autophagy; C57BL mouse; cell line; genetic transfection; genetics; male; metabolism; mouse; non insulin dependent diabetes mellitus; nonobese diabetic mouse; pancreas islet beta cell; pathophysiology; physiology; reporter gene; transgenic mouse; Animals; Autophagy; Cell Line; Diabetes Mellitus, Type 2; Genes, Reporter; Glucose; Insulin; Insulin-Secreting Cells; Kisspeptins; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Transgenic; Proinsulin; Recombinant Proteins; Transfection
Publisher
NATURE PUBLISHING GROUP
Type
journal article
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