The Functional State of Hormone-Sensitive Adenylyl Cyclase Signaling System in Diabetes Mellitus

Alexander O Shpakov,Kira V Derkach

doi:10.1155/2013/594213

Abstract

Diabetes mellitus (DM) induces a large number of diseases of the nervous, cardiovascular, and some other systems of the organism. One of the main causes of the diseases is the changes in the functional activity of hormonal signaling systems which lead to the alterations and abnormalities of the cellular processes and contribute to triggering and developing many DM complications. The key role in the control of physiological and biochemical processes belongs to the adenylyl cyclase (AC) signaling system, sensitive to biogenic amines and polypeptide hormones. The review is devoted to the changes in the GPCR-G protein-AC system in the brain, heart, skeletal muscles, liver, and the adipose tissue in experimental and human DM of the types 1 and 2 and also to the role of the changes in AC signaling in the pathogenesis and etiology of DM and its complications. It is shown that the changes of the functional state of hormone-sensitive AC system are dependent to a large extent on the type and duration of DM and in experimental DM on the model of the disease. The degree of alterations and abnormalities of AC signaling pathways correlates very well with the severity of DM and its complications.

Highlights

Diabetes mellitus (DM) is a major global health problem affecting, according to the World Health Organization, more than 346 million people worldwide [1]
A new view of the nature and pathogenesis of DM-induced complications shared by many specialists nowadays has been prompted by the study of functional activity of hormonal signaling systems regulated by insulin, insulin-like growth factor-1 (IGF-1), and leptin, the principal players responsible for the development of DM and its central and peripheral complications, and by a wide spectrum of other hormones and neurotransmitters, including biogenic amines, purines, glutamate, peptide, and glycoprotein hormones controlling the fundamental cellular processes
This review presents the data concerning the changes in adenylyl cyclase (AC) signaling system sensitive to biogenic amines, peptide hormones, and purines in DM and its complications, such as diabetic encephalopathy, diabetic peripheral neuropathy, diabetic cardiomyopathy, and others

Summary

Introduction

Diabetes mellitus (DM) is a major global health problem affecting, according to the World Health Organization, more than 346 million people worldwide [1]. As was found in our experiments, in the brain tissue of rats with prolonged STZ-induced T1DM, the stimulating effects of PACAP-38, the predominant form of PACAP in mammals, on AC activity and GppNHp binding were significantly decreased and could be largely restored by the longterm treatment with intranasal insulin [32].

Results

Conclusion