Enhanced insulin secretion and glucose tolerance in rats exhibiting low plasma free fatty acid levels and hypertriglyceridaemia due to congenital albumin deficiency

Abstract

Congenitally analbuminaemic individuals and rats (NARs) exhibit several metabolic abnormalities, including hypertriglyceridaemia and plasma free fatty acid deficiency. Our aim was to study glucose homeostasis and insulin secretion in NARs. Plasma concentrations of lipids, glucose and insulin and secretion of insulin from the pancreatic islets were measured in female NARs and control animals (Sprague-Dawley rats; SDRs). Glucose homeostasis tests were also performed. Plasma glucose levels were similar between NARs and SDRs, irrespective of feeding status. However, fed insulinaemia was ∼37% higher (P ≤ 0.05) in NARs than in SDRs. The NARs displayed a markedly increased glucose tolerance, i.e. the integrated glycaemic response was one-third that of the control animals. Enhanced glucose tolerance was associated with threefold higher insulinaemia at peak glycaemia after a glucose load than in the control animals. Similar peripheral insulin sensitivity was observed between groups. Isolated pancreatic islets from NARs secreted significantly more insulin than islets from SDRs in response to a wide range of glucose concentrations (2.8-33.3 mm). Despite having similar liver glycogen contents in the fully fed state, NARs had ∼40% (P ≤ 0.05) lower glycogen contents than SDRs after 6 h fasting. The injection of a gluconeogenic substrate, pyruvate, elicited a faster rise in glycaemia in NARs compared with SDRs. Overall, NARs displayed enhanced glucose tolerance, insulin secretion and gluconeogenic flux. The higher glucose tolerance in NARs compared with SDRs is attributed to enhanced islet responsiveness to secretagogues, while peripheral insulin sensitivity seems not to be involved in this alteration. We propose that the enhanced glucose metabolism is a chronic compensatory adaptation to decreased free fatty acid availability in NARs.

Effect of exercise on body weight and insulin sensitivity following glucose loading in chronic leptin treated rats

“…Insulin levels normally increase following glucose loading, be it oral or intravenous. A similar insulin response to glucose challenge has also been reported before (Figueira, Ribeiro, Ignacio-Sauza, Vercesi, Carneiro & Oliveira, 2012;Harris, 1998). The insulin concentrations in mice that were treated with leptin and challenged with glucose show a same pattern (no different in fasting insulin levels and significant increase after glucose load) with comparable values to the findings in this study (Harris, 1998).…”

Culture Medium Fatty Acid Withdrawal Prompts Insulin Producing Cell Death

“…In the fasted state as well as after a high-fat meal, the increase in the fatty acid/glucose ratio causes glucose oxidation inhibition; the increase in fatty acid oxidation raises citrate concentration and ATP/ADP ratio, which in turn inhibits phosphofructokinase activity and, consequently, the glycolytic pathway [52]. Therefore, in a situation of fatty acid deficiency, an increase in glucose oxidation would be expected, as found and as observed in rats with plasma free fatty acids deficiency [53]. A similar pattern of glucose consumption was observed for lipid synthesis [2].…”

Recurrent Hypoglycemia in a Case of Congenital Analbuminemia

“…Disorders of free fatty acid metabolism are associated with occurrence of hypoglycemia [15]. Studies from analbuminemic rats have shown improved insulin sensitivity, increased insulin secretion, faster depletion of liver glycogen stores during fasting, free fatty acid deficiency with reduced rates of hepatic lipogenesis, triglyceride secretion, and limited lipoprotein lipase activity [4,5]. It is unclear if these abnormalities can contribute to the occurrence of hypoglycemia under certain conditions in humans, but an association of hypoglycemia and low albumin levels has been reported for inpatient medical patients recently [16,17].…”

“…Glucose tolerance tests showed a more rapid return of glucose concentration to normal levels in the analbuminemic rats. ese findings could be attributed to an enhanced islet responsiveness with increased insulin secretion of NAR compared to NR [5].…”