Glucose Tolerance and Insulin Release in Malnourished Rats

Abstract

1. Young Wistar rats were used as an experimental model to determine the effects of protein-energy malnutrition on glucose tolerance and insulin release. 2. Malnourished rats presented some of the features commonly found in human protein-energy malnutrition, such as failure to gain weight, hypoalbuminaemia, fatty infiltration of the liver and intolerance of oral and intravenous glucose loads. 3. The rate of disappearance of glucose from the gut lumen was greater in the malnourished rats but there was no significant difference in portal blood glucose concentration between normal and malnourished rats 5 and 10 min after an oral glucose load. 4. Insulin resistance was not thought to be the cause of the glucose intolerance in the malnourished animals since these rats had a low fasting plasma insulin concentration with a normal fasting blood glucose concentration and no impairment in their hypoglycaemic response to exogenous insulin administration. Furthermore, fasting malnourished rats were unable to correct the insulin-induced hypoglycaemia despite high concentrations of hepatic glycogen. 5. Malnourished rats had lower peak plasma insulin concentrations than normal control animals after provocation with oral and intravenous glucose, intravenous tolbutamide and intravenous glucose plus aminophyllin. This was not due to a reduction in the insulin content of the pancreas or potassium deficiency. Healthy weanling rats, like the older malnourished rats, had a diminished insulin response to intravenous glucose and intravenous tolbutamide. However, their insulin response to stimulation with intravenous glucose plus aminophyllin far exceeded that of the malnourished rats. Thus the impairment of insulin release demonstrated in the malnourished rats cannot be ascribed to a 'functional immaturity' of the pancreas.

Mechanism of impaired glucose tolerance in patients with neoplasia

“…Several previous investigations have failed to demonstrate a protein-losing catabolic state in malignant cachexia (Waterhouse et al, 1951;Fenninger and Mider, 1954;Holroyde et al, 1975 (Sherman et al, 1950). Evidently, protein deprivation in advanced cancer seems to arise not only from anorexia, the major cause of cachexia (Theologides, 1972) but also from monopolization of the host's protein metabolic pool by the tumour tissue (Mider et al, 1948 (Weinkove et al, 1976). This fact, taken in conjunction with our data on glucagon-mediated insulin release in cachectic cancer patients, suggests a similar underlying mechanism for glucose intolerance in human neoplasia.…”

“…Recent studies on malnourished children (Milner, 1971), adults (Smith et al, 1975) and animals (Heard, 1966;Weinkove et al, 1976) conclusively demonstrate that malnutrition can lead to glucose intolerance. In particular the work on malnourished animals (Weinkove et al, 1976) has implicated protein deficiency as an important precursor of impaired carbohydrate metabolism.…”

“…In particular the work on malnourished animals (Weinkove et al, 1976) has implicated protein deficiency as an important precursor of impaired carbohydrate metabolism. For instance, weanling rats fed a protein-deficient diet and challenged with i.v.…”

Serum Insulin-Like Growth Factors I and II Concentrations and Growth Hormone and Insulin Responses to Arginine Infusion in Children with Protein-Energy Malnutrition before and after Nutritional Rehabilitation

“…The low basal insulin levels in kwashiorkor, and the impaired insulin reserve in kwashiorkor and marasmic-kwashiorkor patients can be attributed to the effect of their unbalanced high energy-low protein diet. In support of this view, in experimental animals maintained on low protein diets where the carbohydrate content is necessarily high, plasma insulin levels are consistently low (54,55).…”

Répercussions d'une malnutrition protéino-calorique sur l'homéostase glucidique chez le rat

“…Seule une diminution de la riposte insulinique à une stimulation par le glucose est unanimement admise. Par contre, une controverse persiste à propos des répercussions de la malnutrition sur les réserves pancréatiques en insuline (Levine et al, 1983 ;Weinkove et al, 1976), sur la réponse des cellules B à d'autres stimuli que le glucose (Weinkove et a/., 1976 ;Younoszai and Dixit, 1980) et sur la sensibilité des tissus à l'action de l'insuline (Weinkove et al, 1976 ;Becker, 1983 …”