title: Insulin resistance does not change the ratio of proinsulin to insulin in normal volunteers.
abstract: Plasma glucose, insulin, and proinsulin concentrations were measured before and after an oral glucose challenge in 57 nondiabetic individuals. In addition, insulin-mediated glucose disposal was estimated by determining the steady state plasma glucose (SSPG) concentration after a 180-min iv infusion of somatostatin, insulin, and glucose. The plasma glucose concentration after oral glucose administration was used to divide the population into those with normal (n = 36) or impaired glucose tolerance (IGT; n = 21), and the 36 normal glucose-tolerant individuals were further subdivided into an insulin-sensitive (SSPG, < 9.0 mmol/L; n = 15) and an insulin-resistant (SSPG, > 10 mmol/L; n = 21) group. Fasting and postglucose load insulin concentrations were similar in the normal glucose-tolerant insulin-resistant and IGT groups, but were significantly higher (P < 0.02- < 0.001) than those in normal glucose-tolerant insulin-sensitive individuals. Fasting proinsulin concentrations were also higher (P < 0.002) in the normal glucose-tolerant insulin-resistant (15.1 +/- 1.5 pmol/L) and IGT (15.8 +/- 1.8 pmol/L) groups compared to those in normal glucose-tolerant insulin-sensitive volunteers (9.3 +/- 1.2 pmol/ L). However, the ratio of fasting proinsulin to insulin was identical in all three groups (0.12). When the three groups were combined, significant relationships (P < 0.001) existed between SSPG (degree of insulin resistance) and both fasting proinsulin (r = 0.59) and insulin (r = 0.66) concentrations, but not with the ratio of proinsulin to insulin (r = 0.03). These results demonstrate that fasting proinsulin and insulin concentrations are increased in insulin-resistant, nondiabetic subjects, and the more insulin resistant, the greater the increase. In contrast, the ratio of proinsulin to insulin did not vary as a function of insulin resistance. Thus, neither insulin resistance nor the need to secrete more insulin to maintain glucose tolerance necessarily leads to abnormal insulin processing by the beta-cell.
authors.affiliation: Stanford University School of Medicine, California 94305, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Wang
authors.forename: F
authors.initials: F
authors.lastname: Abbasi
authors.forename: M
authors.initials: M
authors.lastname: Carantoni
authors.forename: Y D
authors.initials: YD
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Azhar
authors.forename: G M
authors.initials: GM
authors.lastname: Reaven
mesh_terms: D000284:Administration, Oral; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011384:Proinsulin / Q000097:blood*; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011384:Proinsulin; D005947:Glucose