This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, P.-W. Articles by Reaven, G. M. Search for Related Content PubMed PubMed Citation Articles by Wang, P.-W. Articles by Reaven, G. M.

Insulin Resistance Does Not Change the Ratio of Proinsulin to Insulin in Normal Volunteers¹

Stanford University School of Medicine, Stanford, California 94305; Geriatric Research, Education, and Clinical Center, Veterans Administration Palo Alto Health Care System, Palo Alto, California 94304; and Shaman Pharmaceuticals, Inc., South San Francisco, California 94080

Address all correspondence and requests for reprints to: G. M. Reaven, M.D., Shaman Pharmaceuticals, Inc., 213 East Grand Avenue, South San Francisco, California 94080-4812.

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 ß-cell.

This article has been cited by other articles:

				N. J. Crowther, N. Cameron, J. Trusler, M. Toman, S. A. Norris, and I. P. Gray Influence of Catch-up Growth on Glucose Tolerance and {beta}-Cell Function in 7-Year-Old Children: Results From the Birth to Twenty Study Pediatrics, June 1, 2008; 121(6): e1715 - e1722. [Abstract] [Full Text] [PDF]

				M. E. Roder and S. E. Kahn Suppression of Beta-Cell Secretion by Somatostatin Does Not Fully Reverse the Disproportionate Proinsulinemia of Type 2 Diabetes Diabetes, December 1, 2004; 53(suppl_3): S22 - S25. [Abstract] [Full Text] [PDF]

				H. J Petrie, S. E Chown, L. M Belfie, A. M Duncan, D. H McLaren, J. A Conquer, and T. E Graham Caffeine ingestion increases the insulin response to an oral-glucose-tolerance test in obese men before and after weight loss Am. J. Clinical Nutrition, July 1, 2004; 80(1): 22 - 28. [Abstract] [Full Text] [PDF]

				A. Tura, G. Pacini, A. Kautzky-Willer, B. Ludvik, R. Prager, and K. Thomaseth Basal and dynamic proinsulin-insulin relationship to assess {beta}-cell function during OGTT in metabolic disorders Am J Physiol Endocrinol Metab, July 1, 2003; 285(1): E155 - E162. [Abstract] [Full Text] [PDF]

				V. Grill, B. Dinesen, S. Carlsson, S. Efendic, O. Pedersen, and C.-G. Ostenson Hyperproinsulinemia and Proinsulin-to-Insulin Ratios in Swedish Middle-aged Men: Association with Glycemia and Insulin Resistance but Not with Family History of Diabetes Am. J. Epidemiol., May 1, 2002; 155(9): 834 - 841. [Abstract] [Full Text] [PDF]

				A. J. G. Hanley, G. McKeown-Eyssen, S. B. Harris, R. A. Hegele, T. M. S. Wolever, J. Kwan, and B. Zinman Cross-Sectional and Prospective Associations between Abdominal Adiposity and Proinsulin Concentration J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 77 - 83. [Abstract] [Full Text] [PDF]

				M. E. Røder, R. S. Schwartz, R. L. Prigeon, and S. E. Kahn Reduced Pancreatic B Cell Compensation to the Insulin Resistance of Aging: Impact on Proinsulin and Insulin Levels J. Clin. Endocrinol. Metab., June 1, 2000; 85(6): 2275 - 2280. [Abstract] [Full Text]

				H. Larsson and B. Ahrén Relative Hyperproinsulinemia as a Sign of Islet Dysfunction in Women with Impaired Glucose Tolerance J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2068 - 2074. [Abstract] [Full Text]