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Biomedical subjects

R W Bilous

Publications and source records attributed to R W Bilous.

61 records · Page 4Linked to original sources
PubMed1980

Human insulin produced by recombinant DNA technology: safety and hypoglycaemic potency in healthy men.

Human insulin synthesised by recombinant DNA technology was compared with highly purified porcine insulin in healthy men. Intracutaneous injection over a wide range of concentrations of both insulins into five subjects gave rise to no local reactions over a 48 h period. The glycaemic response to standard subcutaneous injection at high and low dose levels was measured with both insulins in each of six men. Plasma glucose decrement with the two insulins was similar but human insulin was perhaps slightly more potent than porcine insulin at the low dose, and slightly less so at the high. The glycaemic response to the isulins, each infused intravenously at high and low concentrations for 1 h in a further six subjects, showed a similar trend. Depression of glycaemia with human insulin slightly exceeded that with porcine insulin at the low concentration infusion and fell slightly short of it at the high. Genetically synthesised human insulin seems to be safe and effective in man. Its dose-response relationship may differ from that of porcine insulin.

Adult↗
PubMedDate not supplied

Some lessons from the studies of renal biopsies in patients with insulin-dependent diabetes mellitus.

The authors have studied relationships of renal structure and function in more than 100 patients with insulin-dependent diabetes mellitus (IDDM), aged 13-55 years (mean, 30 years) with diabetes for 1-30 years (mean, 19 years). The authors confirmed the unique nature of the diabetic lesions that, in constellation, occur in no other disease. It was found that increased fractional mesangial volume (Vv Mes) is strongly associated with decreased glomerular filtration rate (GFR), proteinuria, and hypertension and that all patients with overt diabetic nephropathy have Vv Mes in excess of 0.35 micron 3/micron 3. This relationship results from constriction of the capillary lumen and filtration surface as a consequence of increased Vv Mes. Global glomerulosclerosis (scarring) is common in IDDM patients and appears related to arteriolar hyalinosis. Focal segmental glomerulosclerosis is a rare lesion in these patients. Having a single kidney (transplanted IDDM patients) is not associated with accelerated lesion development. The presence or absence of microalbuminuria (MA), per se, does not predict underlying glomerular structure, which may vary from the normal range to a level of pathology bordering on that regularly associated with overt nephropathy. However, when MA is associated with hypertension, or reduced GFR or both, urine albumin excretion (UAE) generally exceeds 40 mg/24 hr, and glomerular pathology is always present. The authors concluded that diabetic nephropathy is a unique renal disorder that cannot be caused by hemodynamic factors alone. The authors further conclude that MA becomes a predictor only when other features of overt nephropathy are already present and that serious diabetic glomerular lesions can be present in patients with normal UAE.

Adolescent↗
PubMedDate not supplied

Biosynthetic human insulin: effect in healthy men on plasma glucose and non-esterified fatty acids in comparison with highly purified pork insulin.

Biosynthetic human insulin (BHI) produced by recombinant DNA technology was administered subcutaneously and intravenously at two dose levels to two groups, each consisting of six normal men. Responses were compared with those for purified pork insulin (PPI) given by the same routes at the same dose levels to the same two groups. The glycemic response to the insulins was similar with a suggestion (seen both with intravenous and subcutaneous administration) that the glycemic depression with BHI was slightly greater at low dose and less at high dose. No significant difference between insulin types was found in the depression of non-esterified fatty acid (NEFA) concentrations, although significant differences between types with low-dose subcutaneous injection emerged during the later phases of the experiment. After termination of high-rate infusion with both insulins, NEFA concentrations rose more rapidly with some overshoot, suggesting that the rate and depth of blood glucose fall in these experiments might have triggered a brisker counterregulatory response. The small differences found between human and pork insulins, although in some cases significant, are unlikely to be of clinical importance.

Adult↗
PubMedDate not supplied

Plasma insulin and C-peptide after subcutaneous and intravenous administration of human insulin (recombinant DNA) and purified porcine insulin in healthy men.

We have compared the plasma profiles of C-peptide, human insulin (recombinant DNA), and purified porcine insulin of pancreatic origin (PPI) in six nondiabetic men after low-dose (4.8 U) or high-dose (9.6 U) subcutaneous injection and low-rate (1.0 U/h) or high-rate (1.7 U/h) intravenous infusion. There was no significant difference in plasma C-peptide or glucose levels when human insulin was compared with PPI at either dose level for subcutaneous injection or intravenous infusion. Thus, there was equal suppression of endogenous insulin by the two species of exogenous insulin. For low-dose subcutaneous injection there was no significant difference between plasma insulin levels of the two species at single time points or when areas were compared. For high-dose subcutaneous injection mean plasma insulin levels were higher after human insulin than after PPI (20-300 min); this serial difference reached conventional statistical significance at 50 min (P less than 0.05) and 90 min (P less than 0.01). For the area under plasma insulin profiles between 0 and 90 min after high-dose s.c. injection, human insulin was higher than PPI (P = 0.06). There was no significant difference between insulin concentrations after human insulin and PPI given by either low- or high-dose intravenous infusion, except that high-dose PPI values (55-110 min) were slightly but significantly higher after high-dose intravenous infusion. Further comparisons of the pharmacokinetics of human and other species of insulin are, therefore, justified in larger numbers of subjects and particularly in diabetic individuals.

Animals↗