Insulin Receptors in Acute Infection: A Study of Factors Conferring Insulin Resistance*

Abstract

Acute infections are accompanied by tissue insulin resistance, as manifested by worsening of metabolic control in diabetic patients and decreased glucose tolerance in non-diabetic subjects. To clarify the potential role of altered insulin receptor status in this phenomenon, we studied [125I]insulin binding to monocytes in 7 otherwise healthy subjects during acute bacterial and viral infections of moderate severity. The values were compared to those obtained after convalescence (five patients) and those of 24 normal subjects. Insulin binding during infection, at a time when insulin resistance was demonstrable, was indistinguishable from convalescent or normal values. Plasma glucose and insulin levels, the insulin to glucose ratio, as well as plasma GH, cortisol, and FFA were significantly elevated during infection, while plasma glucagon, epinephrine, and norepinephrine levels were normal. We conclude that insofar as monocyte receptors are representative of other tissues, insulin resistance in infection is mediated at the postreceptor level.

Severity, Duration, and Mechanisms of Insulin Resistance during Acute Infections*

“…Multiple factors can cause resistance to insulin-stimulated glucose utilization, but the exact cause(s) during infection is not clear. The secretion of insulin antagonistic hormones, such as glucagon (32), cortisol (33,34), GH (2,3,35), increases during infections, although normal concentrations also have been reported (2). Of the antagonistic hormones, glucagon has no insulin antagonistic properties outside of the liver (36), thus excluding it as a cause of impaired glucose utilization.…”

“…The apparent blockade in glucose storage could result from diminished glycogen synthesis, accelerated glycogenolysis, or both. (J Clin Endocrinol Metab 69: 317,1989) T HE OCCURRENCE of insulin resistance during experimental and natural infections is supported by studies demonstrating diminished glucose tolerance and hyperinsulinemia (1)(2)(3)(4). However, the severity and duration of impaired insulin action during acute infections are unknown, since the degree of insulin resistance has not been quantitated or compared to other insulin-resistant states.…”

Associations between lipid metabolism and fertility in the dairy cow

“…Insulin signalling is mainly regulated downstream of the receptor, with high circulating lipid concentrations promoting peripheral insulin resistance. This is a mechanism to decrease glucose uptake into non-essential tissues during nutrient shortage (Drobny et al 1984;White 2006). Plasma growth hormone (GH) secretion peaks at calving or shortly thereafter, then gradually declines (Kawashima et al 2007;Wathes et al 2011).…”

“…Acute infections cause local insulin resistance (Drobny et al 1984) and we have shown previously that a-2-HS-glycoprotein (AHSG) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4), two genes implicated in insulin resistance, are upregulated in the endometrium when cows are in severe NEB, with the expression of both genes showing a significant positive correlation with circulating NEFA concentrations . The main site of AHSG synthesis is the liver, with protein production increasing in response to fat accumulation, which, in turn, inhibits insulin receptor signalling (Stefan et al 2006).…”

Transient Extreme Insulin Resistance in Shoch during Diabetic Ketoacidosis.

“…Other factors include inadequate initial fluid replacement, and the post-insulin receptor resistance to insulin action. The latter may be caused, at least in part, by the presence of severe pulmonary infection [17,18].…”