Abstract Title:

Intermittent Fasting Preserves Beta-Cell Mass in Obesity-induced Diabetes via the Autophagy-Lysosome Pathway.

Abstract Source:

Autophagy. 2017 Aug 30:0. Epub 2017 Aug 30. PMID: 28853981

Abstract Author(s):

Haiyan Liu, Ali Javaheri, Rebecca J Godar, John Murphy, Xiucui Ma, Nidhi Rohatgi, Jana Mahadevan, Krzysztof Hyrc, Paul Saftig, Connie Marshall, Michael L McDaniel, Maria S Remedi, Babak Razani, Fumihiko Urano, Abhinav Diwan

Article Affiliation:

Haiyan Liu


Obesity-induced diabetes is characterized by hyperglycemia, insulin resistance, and progressive beta cell failure. In islets of mice with obesity-induced diabetes, we observe increased beta cell death and impaired autophagic flux. We hypothesized that intermittent fasting, a clinically sustainable therapeutic strategy, stimulates autophagic flux to ameliorate obesity-induced diabetes. Our data show that despite continued high-fat intake, intermittent fasting restores autophagic flux in islets and improves glucose tolerance by enhancing glucose-stimulated insulin secretion, beta cell survival, and nuclear expression of NEUROG3, a marker of pancreatic regeneration. In contrast, intermittent fasting does not rescue beta-cell death or induce NEUROG3 expression in obese mice with lysosomal dysfunction secondary to deficiency of the lysosomal membrane protein, LAMP2 or haplo-insufficiency of BECN1/Beclin-1, a protein critical for autophagosome formation. Moreover, intermittent fasting is sufficient to provoke beta cell death in non-obese lamp2 null mice, attesting to a critical role for lysosome function in beta cell homeostasis under fasting conditions. Beta cells in intermittently-fasted LAMP2- or BECN1-deficient mice exhibit markers of autophagic failure with accumulation of damaged mitochondria and upregulation of oxidative stress. Thus, intermittent fasting preserves organelle quality via the autophagy-lysosome pathway to enhance beta cell survival and stimulates markers of regeneration in obesity-induced diabetes.

Study Type : Animal Study

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