Disordered insulin secretion in the development of insulin resistance and Type 2 diabetes

TY - JOUR

T1 - Disordered insulin secretion in the development of insulin resistance and Type 2 diabetes

AU - Schofield, C. J.

AU - Sutherland, C.

N1 - Copyright 2012 Elsevier B.V., All rights reserved.

PY - 2012

Y1 - 2012

N2 - For many years, the development of insulin resistance has been seen as the core defect responsible for the development of Type2 diabetes. However, despite extensive research, the initial factors responsible for insulin resistance development have not been elucidated. If insulin resistance can be overcome by enhanced insulin secretion, then hyperglycaemia will never develop. Therefore, a ß-cell defect is clearly required for the development of diabetes. There is a wealth of evidence to suggest that disorders in insulin secretion can lead to the development of decreased insulin sensitivity. In this review, we describe the potential initiating defects in Type 2 diabetes, normal pulsatile insulin secretion and the effects that disordered secretion may have on both ß-cell function and hepatic insulin sensitivity. We go on to examine evidence from physiological and epidemiological studies describing ß-cell dysfunction in the development of insulin resistance. Finally, we describe how disordered insulin secretion may cause intracellular insulin resistance and the implications this concept has for diabetes therapy. In summary, disordered insulin secretion may contribute to development of insulin resistance and hence represent an initiating factor in the progression to Type 2 diabetes.

AB - For many years, the development of insulin resistance has been seen as the core defect responsible for the development of Type2 diabetes. However, despite extensive research, the initial factors responsible for insulin resistance development have not been elucidated. If insulin resistance can be overcome by enhanced insulin secretion, then hyperglycaemia will never develop. Therefore, a ß-cell defect is clearly required for the development of diabetes. There is a wealth of evidence to suggest that disorders in insulin secretion can lead to the development of decreased insulin sensitivity. In this review, we describe the potential initiating defects in Type 2 diabetes, normal pulsatile insulin secretion and the effects that disordered secretion may have on both ß-cell function and hepatic insulin sensitivity. We go on to examine evidence from physiological and epidemiological studies describing ß-cell dysfunction in the development of insulin resistance. Finally, we describe how disordered insulin secretion may cause intracellular insulin resistance and the implications this concept has for diabetes therapy. In summary, disordered insulin secretion may contribute to development of insulin resistance and hence represent an initiating factor in the progression to Type 2 diabetes.

UR - https://www.scopus.com/pages/publications/84864025055

U2 - 10.1111/j.1464-5491.2012.03655.x

DO - 10.1111/j.1464-5491.2012.03655.x

M3 - Book/Film/Article review

C2 - 22443306

AN - SCOPUS:84864025055

SN - 0742-3071

VL - 29

SP - 972

EP - 979

JO - Diabetic Medicine

JF - Diabetic Medicine

IS - 8

ER -