Korean Diabetes J.  2009 Dec;33(6):453-457. 10.4093/kdj.2009.33.6.453.

Autophagy in Diabetes

• Jung HS
• Lee MS

• KMID: 2298049
• DOI: http://doi.org/10.4093/kdj.2009.33.6.453

Abstract

Diabetes mellitus is characterized by decreased insulin secretion and action. Decreased insulin secretion results from a reduction in mass and/or function of pancreatic beta-cells. Apoptosis, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress responses have been suggested as mechanisms for the changes in beta-cells in type 2 diabetes; however, the underlying causes have not been clearly elucidated. Autophagy is an intracellular process that maintains cellular homeostasis through degradation and recycling of organelles. Recently, we reported reduction of beta-cell mass in autophagy-deficient mice. Pancreatic insulin content was also decreased due to the decreased beta-cell mass and the reduced number of insulin granules. Morphological analysis of these beta-cells revealed an accumulation of ubiquitinated proteins, swollen mitochondria, and distended ER. Insulin secretory function ex vivo was also impaired. As a result, autophagy-deficient mice showed hypoinsulinemia and hyperglycemia. These results suggested that autophagy is necessary to maintain the structure, mass and function of beta-cells. In addition, as autophagy may play a protective role against ER stress and rejuvenate organelle function, impaired autophagy may lead to mitochondrial dysfunction and ER stress, which have been implicated as causes of insulin resistance. Therefore, in addition to beta-cell homeostasis, dysregulated autophagy may possibly be involved in insulin resistance.

Keyword

Autophagy; Diabetes mellitus; Endoplasmic reticulum; Insulin-secreting cells; Mitochondria

MeSH Terms

Animals
Apoptosis
Autophagy
Diabetes Mellitus
Endoplasmic Reticulum
Homeostasis
Hyperglycemia
Insulin
Insulin Resistance
Insulin-Secreting Cells
Mice
Mitochondria
Organelles
Oxidative Stress
Recycling
Ubiquitinated Proteins
Insulin
Ubiquitinated Proteins

Figure

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  Fig. 1 Adaptive autophagy induced by nutrient deprivation.

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  Fig. 2 Blood glucose and serum insulin levels of β-cell-specific autophagy-deficient mice7).

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  Fig. 3 β-cell mass of β-cell-specific autophagy-deficient , mice7).

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