MitoNEET-Parkin effects in pancreatic α- and β-cells, cellular survival, and intrainsular cross talk

Christine Kusminski, Shiuhwei Chen, Risheng Ye, Kai Sun, Qiong A. Wang, Stephen B. Spurgin, Phillip E. Sanders, Joseph T. Brozinick, Werner J. Geldenhuys, Wen-Hong Li, Roger H Unger, Philipp E Scherer

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Mitochondrial metabolism plays an integral role in glucose-stimulated insulin secretion (GSIS) in β-cells. In addition, the diabetogenic role of glucagon released from α-cells plays a major role in the etiology of both type 1 and type 2 diabetes because unopposed hyperglucagonemia is a pertinent contributor to diabetic hyperglycemia. Titrating expression levels of the mitochondrial protein mitoNEET is a powerful approach to fine-tune mitochondrial capacity of cells. Mechanistically, β-cell-specific mitoNEET induction causes hyperglycemia and glucose intolerance due to activation of a Parkin-dependent mitophagic pathway, leading to the formation of vacuoles and uniquely structured mitophagosomes. Induction of mitoNEET in α-cells leads to fasting-induced hypoglycemia and hypersecretion of insulin during GSIS. MitoNEET-challenged α-cells exert potent antiapoptotic effects on β-cells and prevent cellular dysfunction associated with mitoNEET overexpression in β-cells. These observations identify that reduced mitochondrial function in α-cells exerts potently protective effects on β-cells, preserving β-cell viability and mass.

Original languageEnglish (US)
Pages (from-to)1534-1555
Number of pages22
JournalDiabetes
Volume65
Issue number6
DOIs
StatePublished - Jun 1 2016

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Cell Survival
Insulin
Hyperglycemia
Glucose
Glucose Intolerance
Mitochondrial Proteins
Vacuoles
Glucagon
Type 1 Diabetes Mellitus
Hypoglycemia
Type 2 Diabetes Mellitus

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

MitoNEET-Parkin effects in pancreatic α- and β-cells, cellular survival, and intrainsular cross talk. / Kusminski, Christine; Chen, Shiuhwei; Ye, Risheng; Sun, Kai; Wang, Qiong A.; Spurgin, Stephen B.; Sanders, Phillip E.; Brozinick, Joseph T.; Geldenhuys, Werner J.; Li, Wen-Hong; Unger, Roger H; Scherer, Philipp E.

In: Diabetes, Vol. 65, No. 6, 01.06.2016, p. 1534-1555.

Research output: Contribution to journalArticle

Kusminski, C, Chen, S, Ye, R, Sun, K, Wang, QA, Spurgin, SB, Sanders, PE, Brozinick, JT, Geldenhuys, WJ, Li, W-H, Unger, RH & Scherer, PE 2016, 'MitoNEET-Parkin effects in pancreatic α- and β-cells, cellular survival, and intrainsular cross talk', Diabetes, vol. 65, no. 6, pp. 1534-1555. https://doi.org/10.2337/db15-1323
Kusminski, Christine ; Chen, Shiuhwei ; Ye, Risheng ; Sun, Kai ; Wang, Qiong A. ; Spurgin, Stephen B. ; Sanders, Phillip E. ; Brozinick, Joseph T. ; Geldenhuys, Werner J. ; Li, Wen-Hong ; Unger, Roger H ; Scherer, Philipp E. / MitoNEET-Parkin effects in pancreatic α- and β-cells, cellular survival, and intrainsular cross talk. In: Diabetes. 2016 ; Vol. 65, No. 6. pp. 1534-1555.
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