The fourth Musketeer — from Alexandre Dumas to Claude Bernard

Abstract

Considerations of the pathophysiology of non-insulin dependent diabetes mellitus (NIDDM) usually focus on the respective roles of the so-called triumvirate-beta cell, muscle and liver [1]. Often overlooked in this context is the role of the adipose tissue, and attention is usually addressed to consideration of studies in which isolated adipocytes were used as a surrogate for muscle in studies of insulin action. The goal of this presentation will be to develop a radically different hypothesis, and marshal evidence that it is the loss of normal regulation of adipose tissue that plays the central role in both the hyperglycaemia and the dyslipidaemia that characterizes patients with NIDDM.

The influence of sub‐optimal protein nutrition on insulin hypersecretion evoked by high‐energy/high‐fat feeding in rats

“…Rats that had been maintained on a diet containing the standard amount of protein responded to the challenge of high-energy/high-fat feeding with dramati-cally enhanced insulin secretion. This profile may bear parallels in man, where some insulin-resistant individuals exhibit an enhanced insulin secretory response to maintain normal glucose tolerance [10]. In contrast, rats maintained on low-protein diet prior to transfer to the high-energy/high-fat diet failed to respond with an enhanced insulin secretory response to intravenous glucose.…”

“…It is also not known whether impairments in insulin secretion and action have a causal link [10][11][12]. Measurements of the rate of glucose infusion required to maintain glycaemia and endogenous glucose production and whole-body glucose disposal rates during the euglycaemic-hyperinsulinaemic clamp in the LP group gave no indication that a history of protein malnutrition adversely affects whole-body, hepatic or peripheral insulin action in rats maintained on a high-energy/high-fat diet.…”

The biochemical basis of increased hepatic glucose production in a mouse model of type 2 (non-insulin-dependent) diabetes mellitus

“…However, Figure 3 also shows that there is an increase in intracellular conversion of this amino acid to glucose. Considering all the facts, one can postulate that in obese NIDDM patients, elevated HGP is caused by increased fatty acid oxidation [45,46].…”

Role of insulin in hepatic fatty acid partitioning: emerging concepts

“…In humans, insulin resistance results in derangements of liver metabolism which are associated with such clinically important conditions as obesity, diabetes and atherosclerosis. The perceived role of the liver in the aetiology of these conditions has attracted extensive research in the area, and several reviews have appeared in recent years that deal with aspects of the role of the hormone in the control of liver lipid metabolism (see, e.g., [1][2][3]). The aim of the present one is not to duplicate these, but rather to suggest possible ways in which newly acquired information can be combined with other well-established phenomena in the formulation of an integrated theory of control of the hepatic partitioning of fatty acid metabolism by insulin.…”