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

A1 - Schofield,C. J.

A1 - Sutherland,C.

AU - Schofield,C. J.

AU - Sutherland,C.

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. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

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. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-84864025055&md5=f4861a4ad382179c2dbcefac19ad6a48

U2 - 10.1111/j.1464-5491.2012.03655.x

DO - 10.1111/j.1464-5491.2012.03655.x

M1 - Book/Film/Article review

JO - Diabetic Medicine

JF - Diabetic Medicine

SN - 0742-3071

IS - 8

VL - 29

SP - 972

EP - 979

ER -