title: Parallel changes of proinsulin and islet amyloid polypeptide in glucose intolerance.
abstract: Elevated proinsulin secretion and islet amyloid deposition are both features of Type 2 diabetes but their relationship to beta-cell dysfunction is unknown. To determine if islet amyloid polypeptide (IAPP) secretion is disproportionate with other beta-cell products at any stage of glucose intolerance, 116 subjects were studied. Non-diabetic subjects with equivalent body mass index (BMI) were assigned to three groups, (i) normal fasting glucose, fpg<5.5 mmol l(-1); (ii) intermediate fasting glucose, fpg> or =5.5<6.15 mmol l(-1); (iii) impaired fasting glucose (IFG), fpg> or =6.1<7.0 mmol l(-1). Diabetic subjects were divided according to therapy (9 diet, 19 tablet, and 11 insulin). IAPP, C-peptide and proinsulin were measured fasting and at the end of a 1-h glucose infusion. Fasting C-peptide, IAPP and proinsulin were significantly elevated in the IFG group compared with the other non-diabetic groups (P<0.02); fasting IAPP/C-peptide and proinsulin/C-peptide were 1-2% in all non-diabetic groups. Fasting and 1-h proinsulin and proinsulin/C-peptide were higher in diabetic compared with non-diabetic subjects (P<0.01). IAPP and IAPP/C-peptide in diabetic groups were similar to that in non-diabetic subjects but reduced in the insulin-treated group (P<0.01). Proinsulin was disproportionately increased compared with C-peptide and IAPP in Type 2 diabetes particularly in severe beta-cell failure implying more than one concurrent beta-cell pathology.
authors.affiliation: Diabetes Research Laboratories, Radcliffe Infirmary, Woodstock Road, OX2 6HE, Oxford, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: MacNamara
authors.forename: B A
authors.initials: BA
authors.lastname: Barrow
authors.forename: S E
authors.initials: SE
authors.lastname: Manley
authors.forename: J C
authors.initials: JC
authors.lastname: Levy
authors.forename: A
authors.initials: A
authors.lastname: Clark
authors.forename: R C
authors.initials: RC
authors.lastname: Turner
mesh_terms: D000682:Amyloid / Q000097:blood / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000178:diet therapy / Q000188:drug therapy; D005215:Fasting; D005260:Female; D018149:Glucose Intolerance / Q000097:blood* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D058228:Islet Amyloid Polypeptide; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000097:blood / Q000378:metabolism*; D012016:Reference Values
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D011384:Proinsulin