J R Brennan | PubMed Health

PubMed1987

Prolonged insulin resistance following insulin-induced hypoglycaemia.

Nineteen normal male volunteers underwent a 10-h glucose clamp study to examine the duration and mechanism of insulin resistance after hypoglycaemia. Dextrose delivery by the Biostator to maintain the target blood glucose level fell below baseline 2 h after induction of hypoglycaemia and remained suppressed for at least 7 h after insulin hypoglycaemia. Insulin secretion as manifested by C-peptide levels remained suppressed for 3-4 h after insulin hypoglycaemia despite return of blood glucose to baseline by 90 min. Glucose kinetic data (3-3H-glucose) performed in six of the subjects indicated that the prolonged insulin resistance was due to significantly increased hepatic glucose production and to suppressed glucose utilisation, persisting for at least 4 h after counterregulatory hormone levels had returned to normal. Post-hypoglycaemic insulin resistance as determined by dextrose delivery was markedly attenuated and the rise in hepatic glucose output totally eliminated in five hypopituitary subjects without growth hormone or cortisol responses to hypoglycaemia. We conclude that post-hypoglycaemic insulin resistance occurs in non-diabetic subjects and persists for at least 7 h following hypoglycaemia. This prolonged insulin resistance is largely related to release of growth hormone and cortisol.

Adult↗

PubMed1985

Pump-induced insulin aggregation. A problem with the Biostator.

A fall in plasma IRI despite constant C-peptide levels during prolonged insulin euglycemic clamp studies using the Biostator (Ames Division, Miles Laboratories, Elkhart, Indiana) prompted a meticulous evaluation of the Biostator's insulin delivery system. At slow infusion rates, a striking loss of immunoreactive and biologically active insulin was observed after 6 h of the Biostator run. Studies with labeled insulin indicated that the loss of insulin was not due to adsorption of insulin to the tubing since recovery of labeled insulin was close to 100%. A variety of techniques (gel filtration, polyacrylamide gel electrophoresis, centrifugation, and Coomassie Brilliant Blue protein assay) indicated that the loss of insulin activity was due to insulin coming out of solution. The insoluble nature of the immunologically and biologically inactive insulin was confirmed by centrifugation, i.e., 88% 125I-insulin precipitated into the pellet. The dependency of this loss of insulin activity on flow rate was clearly demonstrable with activity (IRI) less than 20% of expected at flow rates of 2.1 ml/h, and 30% at 4.2 ml/h. Full recovery was observed only with flow rates of 16.8 ml/h or greater. At each flow rate, IRI rose only after delivery of the effluent between the pump and exit port, demonstrating that insulin alteration occurs within the pump assembly presumably from heat-induced aggregation. Investigators employing the Biostator should carefully examine their systems for this time- and flow rate-dependent alteration of insulin. The loss of IRI at low flow rates (low-dose insulin clamp or insulin delivery during basal periods) will profoundly influence data generated from the Biostator.

Adult↗