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G A Shepherd

Publications and source records attributed to G A Shepherd.

6 recordsLinked to original sources
PubMed1982

A comparison of the activity and disposal of semi-synthetic human insulin and porcine insulin in normal man by the glucose clamp technique.

The activity of semi-synthetic human insulin has been compared with porcine insulin in normal man using an euglycaemic glucose clamp at two different insulin infusion rates. In the two hour infusion insulin levels plateaued for both types of insulin at 44-48 mU/l (infusion rate 0.05 U kg body weight-1 h-1) and 22-24 mU/1 (0.02 U kg-1 h-1), giving identical metabolic clearance rates. The glucose delivery required to maintain euglycaemia in the second hour of insulin infusion was 13.9 +/- 2.1 g (mean +/- SEM) and 14.7 +/- 1.5 g (NS) at the lower dose for porcine and human insulins respectively, and 27.1 +/- 2.5 and 28.0 +/- 2.9 g (NS) at the higher dose. The potency ratio for human, compared with porcine, insulin was 1.06 +/- 0.12. No differences were seen in the time of onset of action of the insulins, serum half-life or distribution space. The responses of blood lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate were identical. No untoward reactions occurred. The activity and disposal of this semi-synthetic human insulin are indistinguishable from porcine insulin in normal euglycaemic man.

Adult↗
PubMed1982

Impaired subcutaneous absorption of insulin in 'brittle' diabetics.

Twenty-four hour plasma free insulin and blood glucose and intermediary metabolite profiles have been measured in 6 C-peptide deficient 'brittle' diabetic patients, during continuous sc and im insulin infusion. During sc infusion free insulin profiles were erratic and unpredictable. Mean 24 h blood glucose levels were raised at 12.6 +/- 2.1 (SE) mmol/l, and 3-hydroxybutyrate at 0.24 +/- 0.08 mmol/l. Blood lactate (1.88 +/- 0.18 mmol/l) and glycerol (0.084 +/- 0.007) were also elevated. Insulin (im) restored free insulin profiles to the normal pattern as found in 'stable' diabetics on sc infusion, with characteristic post-meal peaks (49 +/- 7, 103 +/- 35, and 95 +/- 34 mU/l) and stable night-time levels. Mean 24 h blood glucose was 6.7 +/- 1.1 mmol/l (P less than 0-.05 compared to sc infusion) and 3-hydroxybutyrate 0.07 +/- 0.02 mmol/l (P less than 0.05). Blood lactate (1.67 +/- 0.08 mmol/l) and glycerol (0.10 +/- 0.02 mmol/l) levels remained abnormal. The ratio of plasma free insulin to insulin dose administered was significantly higher during im infusion. In the 6 'stable' diabetics on sc insulin infusion good blood glucose control (7.1 +/- 0.9 mmol/l) was accompanied by clear post-prandial insulin peaks, and stable nocturnal levels. The results strongly suggest that in one category of 'brittle' diabetics there is defective and erratic sc insulin absorption.

3-Hydroxybutyric Acid↗
PubMedDate not supplied

Comparison of the activity and pharmacokinetics of porcine insulin and human insulin (Novo) as assessed by the glucose clamp technique in normal and diabetic man.

Using the glucose clamp technique, human insulin (Novo) and natural porcine insulin were found to have identical potency in terms of glucose delivery in the second hour of i.v. infusion at low (0.02 U/kg/h; 265 +/- 25 versus 232 +/- 35 mg/min, respectively) and high (0.05 U/kg/h; 467 +/- 47 versus 452 +/- 41 mg/min, respectively) doses in normal man. Insulin metabolic clearance rates, serum in vivo half-life, and rate of onset of action were also similar. In insulin-dependent diabetic subjects, whose blood glucose levels were also held constant by feedback glucose infusion, the free insulin profiles after s.c. injection of neutral soluble human insulin and porcine insulin (0.2 U/kg) were identical, and similar to those after conventional and highly purified bovine insulin preparations. Glucose requirement to maintain normoglycemia for the first 5 h after injection was 49.6 +/- 8.2 g for conventional bovine insulin, 50.4 +/- 10.0 g for highly purified bovine, 40.5 +/- 6.9 g for human insulin, and 50.6 +/- 12.4 g for porcine insulin (NS by analysis of variance). No difference in insulin activity was detected when glucose requirement was expressed in terms of the prevailing free insulin concentration. Responses of blood intermediary metabolite levels were indistinguishable between all insulins in both studies.

Adult↗