title: Relationships among age, proinsulin conversion, and beta-cell function in nondiabetic humans.
abstract: The aim of the present study was to examine the relationships among beta-cell function, proinsulin conversion to insulin, and age. We studied insulin and proinsulin secretion in nondiabetic subjects during an oral glucose tolerance test (OGTT) using published indexes of beta-cell function (n = 379, age 16--68 years) and a modified hyperglycemic clamp (10 mmol/l, additional glucagon-like peptide [GLP-1] infusion, final arginine bolus; n = 50, age 19--68 years). Proinsulin conversion to insulin was assessed using proinsulin/insulin (PI/I) ratios immediately after an acute stimulus (OGTT, 30 min; hyperglycemic clamp, 2.5-5.0 min after glucose and arginine). There was a negative correlation between age and beta-cell function (adjusted for insulin sensitivity, BMI, and fasting glucose) in the OGTT (r = -0.21, P < 0.001) and first phase of the hyperglycemic clamp (r = -0.30, P = 0.03), but not second phase (r = -0.08, P = 0.6) or arginine-induced insulin secretion (r = 0.06, P = 0.7). There was a positive correlation between age and the PI/I ratio in the OGTT (r = 0.24, P < 0.001). Analogously, there was also a positive correlation between age and the PI/I ratio during first phase (r = 0.37, P = 0.009) and arginine stimulation (r = 0.33, P = 0.01) of the hyperglycemic clamp. First-phase insulin secretion of the hyperglycemic clamp was inversely correlated with the PI/I ratio (r = -0.60, P < 0.001). Interestingly, adjusting first-phase secretion rate for the PI/I ratio abolished the linear relationship with age (r = -0.06, P = 0.7). In conclusion, aging is associated with deteriorating beta-cell function and deteriorating proinsulin conversion to insulin. The age effect on insulin secretion appears to be attributable at least in part to an impairment of proinsulin conversion to insulin.
authors.affiliation: Medizinische Klinik, Abteilung für Endokrinologie, Stoffwechsel und Pathobiochemie, Eberhard-Karls-Universität, Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Alexander
authors.initials: A
authors.lastname: Madaus
authors.forename: Norbert
authors.initials: N
authors.lastname: Stefan
authors.forename: Otto
authors.initials: O
authors.lastname: Tschritter
authors.forename: Elke
authors.initials: E
authors.lastname: Maerker
authors.forename: Anna
authors.initials: A
authors.lastname: Teigeler
authors.forename: Hans
authors.initials: H
authors.lastname: Häring
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
mesh_terms: D000328:Adult; D000367:Age Factors; D003920:Diabetes Mellitus; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000378:metabolism*
chemical_list: D007328:Insulin; D011384:Proinsulin