The role of autophagy in pancreatic β-cell and diabetes

• Published in: Autophagy Vol. 5; no. 2; pp. 280 - 282
• Main Authors: Fujitani, Yoshio, Kawamori, Ryuzo, Watada, Hirotaka
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 16.02.2009
• Subjects: Animals; Autophagy; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Shape; Cycle; Diabetes Mellitus - pathology; Insulin Resistance; Insulin-Secreting Cells - pathology; Landes; Mice; Organogenesis; Phagosomes - metabolism; Phagosomes - pathology; Proteins
• ISSN: 1554-8627; 1554-8635
• DOI: 10.4161/auto.5.2.7656

Pancreatic β-cells play a key role in glucose homeostasis in mammals. Although large-scale protein synthesis and degradation occur in pancreatic β-cells, the mechanism underlying dynamic protein turnover in β-cells remains largely unknown. We found low-level constitutive autophagy in β-cells of C57BL/6 mice fed a standard diet; however, autophagy was markedly upregulated in mice fed a high-fat diet. β-cells of diabetic db/db mice contained large numbers of autophagosomes, compared with non-diabetic db/misty controls. The functional importance of autophagy was analyzed using β-cell-specific Atg7 knockout mice. Autophagy-deficient mice showed degeneration of β-cells and impaired glucose tolerance with reduced insulin secretion. While a high-fat diet stimulated β-cell autophagy in control mice, it induced a profound deterioration of glucose intolerance in β-cell autophagy-deficient mutants, partly because of the lack of a compensatory increase in β-cell mass. These results suggest that the degradation of unnecessary cellular components by autophagy is essential for maintenance of the architecture and function of β-cells. Autophagy also serves as a crucial element of stress responses to protect β-cells under insulin resistant states. Impairment of autophagic machinery could thus predispose individuals to type 2 diabetes.