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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.

Philip Home, G. A. A. Shepherd, George A. Noy, Massimo Massi‐Benedetti, I. Hanning, J. M. Burrin, K. G. M. M. Alberti

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Abstract

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.

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What this paper is about

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.

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Available abstract

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.

Key concepts: Insulin, Internal medicine, Endocrinology, Diabetes mellitus, Medicine, Human insulin, Pharmacokinetics, Potency

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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. — Research Paper | ScholarLens