AUTOPHAGY and DIABETES MELLITUS......new promising concept

Although the body of evidence is still small, relative autophagy insufficiency may be involved in the exacerbation of diabetic microangiopathy and organ damage, and several medications have the potential to activate autophagy. The authors therefore expect that autophagy activation will become a potential therapy to combat diabetic microangiopathy and organ damage. However, at present, there are a couple of major problems to be resolved as described below.

Further examinations are needed to conclude whether autophagy activation is a safe therapy for any kidney diseases, since some reports have suggested that autophagy activation was associated with tubular cell damages in some acute kidney injury models.

The role of autophagy in the development of diabetes is still under debate. Some investigators have shown that pancreatic β-cell-specific autophagy-deficient mouse developed glucose intolerance [89, 90], whereas others have reported that autophagy activation led to β-cell apoptosis. Furthermore, recent interesting studies have shown that genetic inhibition of autophagy in adipose tissue, skeletal muscle, and liver prevented the development of high-fat diet-induced obesity. Therefore, it remains unclear whether autophagy activation shows a health beneficial effect in all stages of diabetic diseases, from the onset of diabetes mellitus to the progression of diabetic complications.

In the past decade, several genetic links have emerged between autophagy deficiency and cancer development, providing increasing support for the concept that autophagy is a tumor suppressor pathway. In contrast, several studies have shown that genetic or pharmacological inhibition of autophagy enhances cytotoxicity of cancer chemotherapeutic agents. The incidence rate of malignant disorder is higher in patients with diabetes. Thus, further examinations regarding the pathogenic and therapeutic roles of autophagy in cancer biology are required.

We have no technical tool to detect autophagy activity in the kidney of humans; therefore, the discovery of a biomarker for autophagy activity with serum and/or urine samples is urgently needed. Finally, no drug has been discovered that can activate autophagy without adverse effects.

When the abovementioned problems are overcome, autophagy regulation may be an effective therapeutic target for diabetic microangiopathy and organ damage. We hope this review has been helpful to researchers interested in autophagy and diabetic microangiopathy and organ damage.