10 research outputs found
Towards peakless, reproducible and long-acting insulins. An assessment of the basal analogues based on isoglycaemic clamp studies
Comparison of the effects on glucose and lipid metabolism of equipotent doses of insulin detemir and NPH insulin with a 16-h euglycaemic clamp
Aims/hypothesis: The association of insulin detemir with non-esterified fatty acid binding sites on albumin may limit its transfer from the circulation into the extravascular extracellular space in adipose tissue and muscle, due to the capillary endothelial cell barrier. In the liver, the open sinusoids may expose hepatocytes to insulin detemir, enabling it to have a greater effect in the liver than in peripheral tissues. Methods: We investigated the effects of equipotent doses of insulin detemir and NPH insulin on hepatic glucose rate of appearance (R-a), peripheral glucose rate of disposal (R-d) and glycerol R-a (a measure of lipolysis) using stable isotope techniques. We also investigated the effects of these insulins on NEFA concentrations in seven healthy volunteers during a 16-h euglycaemic clamp. A higher dose of insulin detemir was also studied. Results: There was no difference in the glucose infusion profile between insulin detemir and NPH. Insulin detemir had a greater effect on mean suppression of glucose R-a (mean difference 0.24 mg kg(-1) min(-1); CI 0.09-0.39; p < 0.01), and minimum glucose R-a, with minimum low dose detemir -0.10 +/- 0.15 mg.kg(-1).min(-1) and minimum NPH 0.17 +/- 0.10 mg.kg(-1).min(-1) (p < 0.02). However, it had a lesser effect on mean suppression of NEFA concentrations (mean difference -0.10 mmol/l; CI -0.03 to -0.17; ANOVA, p < 0.02) than NPH. The effect of insulin detemir on glucose R-d and glycerol R-a was not different from NPH. Following high-dose detemir, total glucose infused and maximum glucose R-d were higher (p < 0.02, p < 0.03) and plasma NEFA concentrations lower (p < 0.01) than with low-dose determir. Conclusions/interpretation: This study suggests that insulin detemir, when compared to NPH insulin, has a greater effect on the liver than on peripheral tissues and thus has the potential to restore the physiological insulin gradient
Treatment with human growth hormone in patients with Prader-Labhart-Willi syndrome reduces body fat and increases muscle mass and physical performance
Effect of the long-acting insulin analogues glargine and degludec on cardiomyocyte cell signalling and function
A Decrease in the Dose of Pegvisomant was Needed for the Treatment of Acromegaly after Adrenalectomy in a Patient with Coexisting Preclinical Cushing's Syndrome
Soluble insulin analogs combining rapid- and long-acting hypoglycemic properties – From an efficient E. coli expression system to a pharmaceutical formulation
Insulin analogs: Assessment of insulin mitogenicity and IGF-I activity.
The metabolic activity of insulin has been studied extensively in vitro and in vivo, based on the initial assessment of insulin receptor affinity, followed by methods to estimate the metabolic activity in vitro. These estimates provide some guidance about the biological activity which will be found in vivo; they need to be confirmed and supplemented by testing the glucose-lowering activity in animals (mice, rats, dogs, pigs). The biological effects (hypoglycemic activity) are related to the direct activation of the insulin receptor and subsequent signaling through intracellular mechanisms. The second group of biological effects is related to cell proliferation (mitogenic activity), which may be mediated by the insulin receptor, by the IGF-I receptor, and by hybrids of the two receptors. The evaluation of the relevance of mitogenicity estimates may be performed in in vitro and in vivo. One approach is cell proliferation in benign and malignant cell lines, for example, on mammary epithelial cell lines MCF-10 and MCF-7 (Milazzo et al. 1997)