Insulin deficiency and insulin resistance in the pathogenesis of NIDDM: is a divorce possible?

Either more complex interactions are at play in the genesis of NIDDM, or a systematic error exists in the approach to investigate the regulation of glucose homeostasis.

Abstract

It is astonishing, even saddening, that after decades of intensive investigation it is still a matter of controversy whether a beta-cell defect or a defective insulin action is the main pathogenic mechanism in insulin-dependent diabetes mellitus (NIDDM) [1][2][3][4].Categoric statements as to the primacy of one or other defect have engrossed the bibliography of many distinguished diabetologists (including yours faithfully).The controversy may have not been futile since it has promoted intensive research into the mechanisms of insulin secretion and of insulin action.Yet, we still seem relatively far from fully understanding the cell biological events, not to mention the molecular ones, that lead to loss of control over glucose homeostasis.The difference with the advances made in the pathogenesis of insulin-dependent diabetes (IDDM) is striking.Barring the option that only second-rate scientists were attracted to NIDDM (an option refused by my logic and instinct of preservation alike!), either more complex interactions are at play in the genesis of NIDDM, or a systematic error exists in our approach to investigate the regulation of glucose homeostasis.Can insulin deficiency or insulin resistance, alone, produce NIDDM?This is a rhetorical question, since a minimal knowledge of physiology dictates that to keep glucose metabolism normally insulin must not only be present, but also be able to exert its action.Thus, if extreme ends are considered, pancreatectomized patients or lean patients with severe