Distribution and kinetics of amylin in humans.

The aim of the study was to determine the apparent volume of distribution (VTOT), total body clearance (CL), fractional clearance, and mean residence time (MRT) of the β-cell hormone amylin. We therefore performed an intravenous injection of 50 μg of human synthetic amylin (amlintide) in nine healthy male subjects during suppression of endogenous amylin release by intravenous somatostatin (0.06 μg ⋅ kg-1 ⋅ min-1). The plasma levels of amylin concentrations over time were analyzed using three-exponential curves. VTOT was 173 ± 16 ml/kg and was not different from that of insulin reported in the literature (157 ml/kg). MRT was 27.7 ± 2.1 min and thus two times the reported value for insulin (14.1 min) and C-peptide (16.4 min). CL and fractional CL were 6.2 ± 0.2 ml ⋅ kg-1 ⋅ min-1and 0.038 ± 0.003 min-1, respectively. Fractional CL is therefore definitely lower than that reported for insulin (0.12-0.2 min-1) but is, however, in the range of that of C-peptide (0.05 min-1). In conclusion, clearance of amylin is similar to that reported for C-peptide and much slower than insulin, indicating that the commonly used molar insulin-to-amylin ratio does not reflect the correct relationship of the two peptides.

[1]  C Cobelli,et al.  The kinetics of insulin in man. II. Role of the liver. , 1987, Diabetes/metabolism reviews.

[2]  D. A. Trainor,et al.  Development of sensitive immunoassays to detect amylin and amylin-like peptides in unextracted plasma. , 1996, Clinical chemistry.

[3]  C Cobelli,et al.  Insulin Secretion and Hepatic Extraction in Humans by Minimal Modeling of C-Peptide and Insulin Kinetics , 1988, Diabetes.

[4]  G. Cooper,et al.  Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro , 1988, Nature.

[5]  T. Ciaraldi,et al.  In Vitro Effects of Amylin on Carbohydrate Metabolism in Liver Cells , 1992, Diabetes.

[6]  D. Steiner,et al.  Lack of Islet Amyloid Polypeptide Regulation of Insulin Biosynthesis or Secretion in Normal Rat Islets , 1990, Diabetes.

[7]  Bruce H. Frank,et al.  Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. , 1986, The Journal of clinical investigation.

[8]  J. Rothbard,et al.  Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[9]  G. Pacini,et al.  Increased levels of circulating islet amyloid polypeptide in patients with chronic renal failure have no effect on insulin secretion. , 1994, The Journal of clinical investigation.

[10]  M. Nakazato,et al.  Islet Amyloid Polypeptide Response to Glucose, Insulin, and Somatostatin Analogue Administration , 1990, Diabetes.

[11]  Michael W. Schwartz,et al.  Evidence of Cosecretion of Islet Amyloid Polypeptide and Insulin by β-Cells , 1990, Diabetes.

[12]  I. Macdonald,et al.  Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men with IDDM , 1997, Diabetologia.

[13]  T. Rink,et al.  Amylin and insulin in rat soleus muscle: dose responses for cosecreted noncompetitive antagonists. , 1992, The American journal of physiology.

[14]  K Thomaseth,et al.  Integrated mathematical model to assess beta-cell activity during the oral glucose test. , 1996, The American journal of physiology.

[15]  S. Bloom,et al.  Very high concentrations of islet amyloid polypeptide are necessary to alter the insulin response to intravenous glucose in man. , 1992, The Journal of clinical endocrinology and metabolism.

[16]  J. Clore,et al.  Amylin/insulin secretory ratios in morbidly obese man: inverse relationship with glucose disappearance rate. , 1994, The Journal of clinical endocrinology and metabolism.

[17]  R. Turner,et al.  Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[18]  G. Cooper,et al.  Amylin injection causes elevated plasma lactate and glucose in the rat , 1991, FEBS letters.

[19]  M Berman,et al.  A model of the kinetics of insulin in man. , 1974, The Journal of clinical investigation.

[20]  Petre Stoica,et al.  Decentralized Control , 2018, The Control Systems Handbook.

[21]  G. Cooper.  Amylin compared with calcitonin gene-related peptide: structure, biology, and relevance to metabolic disease. , 1994, Endocrine reviews.

[22]  K. Alberti,et al.  Acute effects of the human amylin analog AC137 on basal and insulin-stimulated euglycemic and hypoglycemic fuel metabolism in patients with insulin-dependent diabetes mellitus. , 1996, The Journal of clinical endocrinology and metabolism.

[23]  B. Ludvik,et al.  Reduced islet-amyloid polypeptide in insulin-dependent diabetes mellitus , 1990, The Lancet.

[24]  T. Rink,et al.  Selective amylin antagonist suppresses rise in plasma lactate after intravenous glucose in the rat , 1994, FEBS letters.

[25]  C. Wernstedt,et al.  A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas. , 1986, Biochemical and biophysical research communications.

[26]  B. Ludvik,et al.  Decrease of Stimulated Amylin Release Precedes Impairment of Insulin Secretion in Type II Diabetes , 1991, Diabetes.

[27]  Karl Thomaseth,et al.  Amylin release during oral glucose tolerance test. , 1997 .