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The effects of biosynthetic human proinsulin on carbohydrate metabolism
- Source :
- Diabetes. 33(8)
- Publication Year :
- 1984
-
Abstract
- Large quantities of biosynthetic human proinsulin have recently become available through recombinant DNA technology. Since the in vivo effects of human proinsulin have not been studied in man, we compared the dose-response relationship for stimulation of glucose disposal and suppression of hepatic glucose output by proinsulin and insulin. Ten normal subjects were studied using the euglycemic glucose clamp technique. The human proinsulin and insulin infusion rates were chosen to achieve steady-state proinsulin levels 10-fold higher than insulin levels on a molar basis, based on previous observations that porcine proinsulin has ∼10% the potency of insulin. Proinsulin infusion rates of 2.75, 7.5, 22.5, and 45 μg/m2/min were compared with insulin infusion rates of 0.63,1.67, 5, and 10 μg/ m2/min. Primed, continuous infusions of insulin yielded steady-state levels within 25 min, whereas proinsulin levels did not reach a steady state for 120–180 min. The metabolic clearance rate of insulin was 11–12 ml/kg/min at the lower infusion rates but fell to 8.4 ml/kg/min at the highest infusion rate. The metabolic clearance rate of proinsulin was 3.0–3.5 ml/kg/ min at all infusion rates. Dose-response analysis demonstrated that proinsulin-mediated glucose disposal was ∼8% that of insulin. In contrast, proinsulin-mediated suppression of hepatic glucose output was ∼12% that seen with insulin. We conclude that: (1) primed, continuous infusions of proinsulin and insulin have considerably different kinetics; (2) the metabolic clearance rate of proinsulin is only −28% that of insulin, but the processes responsible for removal of insulin from the circulation are more saturable than those responsible for removal of proinsulin; and (3) proinsulin appears to exert a greater effect on hepatic than on peripheral tissues.
- Subjects :
- Adult
Blood Glucose
Male
endocrine system
medicine.medical_specialty
endocrine system diseases
Metabolic Clearance Rate
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Radioimmunoassay
Carbohydrate metabolism
Biology
digestive system
chemistry.chemical_compound
Internal medicine
Insulin Secretion
Internal Medicine
medicine
Humans
Insulin
Proinsulin
C-Peptide
C-peptide
nutritional and metabolic diseases
Metabolism
Glucose clamp technique
Carbohydrate
Endocrinology
chemistry
Liver
Female
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 00121797
- Volume :
- 33
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....12165046f03a9ce14ffe2ea4d457274f