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Insulin resistance, impaired glucose tolerance and non-insulin-dependent diabetes, pathologic mechanisms and treatment: Current status and therapeutic possibilities

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Progress in Drug Research

Part of the book series: Progress in Drug Research ((PDR,volume 51))

Summary

Impaired glucose tolerance and non-insulin-dependent diabetes (NIDDM) are the pathologic consequences of two co-incident and interacting conditions, namely insulin resistance and relative insulin deficiency. Recognised by the World Health Authority as a global health problem there are at 1995 estimates at least 110 million diagnosed diabetics world wide with at least the same number undiagnosed. Diabetes is the 4th leading cause of death in developed countries and its management exerts a vast economic and social burden. Insulin resistance is established as the characteristic pathologic feature of patients with glucose intolerance and NIDDM describing a state in which insulin stimulated glucose uptake and utilisation in liver, skeletal muscle and adipose tissue is impaired and coupled to impaired suppression of hepatic glucose output. Although the biochemical mechanisms underpinning both defects are becoming better understood, the genetic and molecular causes remain elusive; and whether insulin resistance or relative insulin deficiency represents the primary defect in patients with NIDDM is the matter of some debate. In this article we review the biochemical and molecular nature of the defects in insulin sensitivity and glucose uptake, and discuss some of the potential causative mechanisms. The genetic and environmental basis of insulin resistance is reviewed and presented, and potential therapeutic targets including thiazolidinediones are discussed.

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Abbreviations

NIDDM:

non-insulin dependent diabetes

IGT:

impaired glucose tolerance

HGP:

hepatic glucose production

TNFα:

tumor necrosis factor α

WHO:

World Health Organization

WHR:

waist-to-hip ratio

OGIT:

oral glucose tolerance test

BMI:

body mass index

MRI:

magnetic resonance imaging

FFA:

free fatty acids

LPL:

lipoprotein lipase

ZDF:

diabetic obese Zucker rat

IDDM:

insulin dependent diabetes

GFAT:

glutamine fructose 6-phosphate amido transferase

PEPCK:

phosphoenolpyruvate carboxykinase

MODY:

Maturity Onset Diabetes in the Young

HNF:

hepatic nuclear factor

US:

United States

PPARγ:

peroxisome proliferator activated receptor-γ

PPARα:

peroxisome proliferator activated receptor-α

FDA:

food and drugs authority

NDA:

new drug application

DHEA:

dehydroepiandrosterone

ACTH:

adrenocorticotrophic hormone

MC2:

melanocortin receptor 2

PVN:

paraventricular nucleus

phen:

phentermine

fen:

fenfluramine

5-HT:

5 hydroxytryptamine

D:

dopamine

NAASCO:

North American Association for the Study of Obesity

BAT:

brown adipose tissue

UCP:

uncoupling protein

QTL:

quantitative trait locus

GDP:

guanosine diphosphate

GABA:

γ-aminobutyric acid

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    Nicholas C. Turner & John C. Clapham

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Turner, N.C., Clapham, J.C. (1998). Insulin resistance, impaired glucose tolerance and non-insulin-dependent diabetes, pathologic mechanisms and treatment: Current status and therapeutic possibilities. In: Jucker, E. (eds) Progress in Drug Research. Progress in Drug Research, vol 51. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8845-5_2

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