Insulin and insulin resistance

Abstract

As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalization, urbanisation and industrialization have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits.

Figure 1

Schematic presentation of insulin secretory pathways. Adapted from references: & . Footnotes: Figure Abbreviations Akt/PKB = protein kinase B GLP-1 = glucagon-like peptide 1 ATP = adenosine triphosphate IRS = insulin receptor substrate ADP = adenosine diphosphate MAP kinase = mitogen activated protein kinase cAMP= cyclic adenosine monophosphate PACAP = pituitary adenylate cyclase-activating polypeptide DAG = diacylglycerol PI3K = phosphatidylinositol 3-kinase GIP = gastric inhibitory peptide / PIPD1 & 2 = phosphatidylinositol dependent protein kinases 1 & 2 glucose-dependent insulinotropic polypeptide PKC = protein kinase C Glucose- 6- P = glucose 6 phosphate RAS = rat sarcoma protein GLUT 2 = glucose transport protein 2 SHC =adaptor protein with src-homology GLUT 4 = glucose transport protein 4 VIP= vasoactive intestinal peptide

Figure 2

Schematic presentation of insulin signalling pathways. Adapted from references: , & . Footnotes: Figure Abbreviations Akt/PKB = protein kinase B GLP-1 = glucagon-like peptide 1 ATP = adenosine triphosphate IRS = insulin receptor substrate ADP = adenosine diphosphate MAP kinase = mitogen activated protein kinase cAMP= cyclic adenosine monophosphate PACAP = pituitary adenylate cyclase-activating polypeptide DAG = diacylglycerol PI3K = phosphatidylinositol 3-kinase GIP = gastric inhibitory peptide / PIPD1 & 2 = phosphatidylinositol dependent protein kinases 1 & 2 glucose-dependent insulinotropic polypeptide PKC = protein kinase C Glucose- 6- P = glucose 6 phosphate RAS = rat sarcoma protein GLUT 2 = glucose transport protein 2 SHC =adaptor protein with src-homology GLUT 4 = glucose transport protein 4 VIP= vasoactive intestinal peptide