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Effects of the amylin analogue pramlintide on hepatic glucagon responses and intermediary metabolism in Type 1 diabetic subjects
Author(s) -
Ørskov L.,
Nyholm B.,
Hove K. Yde,
Gravholt C. H.,
Møller N.,
Schmitz O.
Publication year - 1999
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1046/j.1464-5491.1999.00162.x
Subject(s) - glucagon , medicine , endocrinology , amylin , insulin , glycogen , basal (medicine) , pancreatic hormone , diabetes mellitus , insulin resistance , islet
Summary Aims Hepatic glycogen stores have been shown to be depleted, and glucagon stimulated hepatic glucose production reduced, in Type 1 diabetic subjects. Co‐administration of amylin and insulin has been shown to replete hepatic glycogen stores in diabetic animal models. The aim of the present study was to investigate the effect of amylin replacement on hepatic glucagon responsiveness in humans. Methods Thirteen Type 1 diabetic men were studied in a double‐blind, placebo‐controlled, cross‐over study after 4 weeks of subcutaneous pramlintide (30 μg q.i.d.) or placebo administration. Following an overnight fast, plasma glucose was kept above 5 mmol/l (baseline 210–240 min) with an insulin infusion rate of 0.25 mU.kg –1 .min –1 . To control portal glucagon levels, somatostatin was infused at a rate of 200 μg/h. Basal growth hormone (2 ng.kg –1 .min –1 ) and glucagon (0.7 ng.kg –1 .min –1 ) were replaced. Glucagon infusion was increased to 2.1 ng.kg –1 .min –1 at 240–360 min (step 1) and to 4.2 ng.kg –1 .min –1 at 360–420 min (step 2). Results Baseline plasma glucose (5.59 ± 0.16 vs. 5.67 ± 0.25 mmo/l) and endogenous glucose production (EGP) (1.32 ± 0.22 vs. 1.20 ± 0.13 mg.kg –1 . min –1 ) were similar and the response to glucagon was unaffected by pramlintide (glucose: step 1; 6.01 ± 0.31 vs. 5.94 ± 0.38 mmo/l, step 2; 6.00 ± 0.37 vs. 5.96 ± 0.50 mmol/l, EGP: step 1; 1.91 ± 0.18 vs. 1.83 ± 0.15 mg.kg –1 .min –1 , step 2; 2.08 ± 0.17 vs. 1.96 ± 0.16 ng.kg –1 .min –1 , pramlintide vs. placebo). Glucose disposal rates were similar at baseline (2.44 ± 0.13 vs. 2.28 ± 0.09 mg.kg –1 .min –1 , pramlintide vs. placebo) as well as during the glucagon challenge ( P ‐values all > 0.2). Conclusions Co‐administration of pramlintide and insulin to Type 1 diabetic subjects for 4 weeks does not change the plasma glucose or endogenous glucose production response to a glucagon challenge, following an overnight fast. In addition, pramlintide administration does not appear to alter insulin‐mediated glucose disposal.