| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print August 6, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00093.2002
Submitted on March 1, 2002
Accepted on July 16, 2002
1 Institute of Systems Science and Biomedical Engineering, National Research Council, Padova, Italy
2 Department of Medicine M (Endocrinology and Diabetes), University Hospital of Aarhus, Aarhus, Denmark
3 Department of Internal Medicine, University of Pisa, Pisa, Italy; Department of Internal Medicine, University of Pisa, Pisa, Italy
4 Department of Internal Medicine, University of Pisa, Pisa, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy
* To whom correspondence should be addressed. E-mail: mari{at}ladseb.pd.cnr.it.
We investigated ß-cell function and its relationship with insulin sensitivity in 17 normal volunteers. For insulin secretion (by C-peptide deconvolution), a mathematical model was applied to 24-hr triple-meal tests (MT) as well as oral glucose tolerance tests (OGTT); insulin sensitivity was assessed by the euglycemic insulin clamp technique. The ß-cell model featured: a glucose concentration-insulin secretion dose-response (characterized by secretion at 5 mM glucose and slope), a secretion component proportional to the glucose concentration derivative, and a time-dependent potentiation factor (modulating the dose-response and accounting for effects of sustained hyperglycemia and incretins). The ß-cell dose-response functions estimated from the whole 24-hr MT, the first 2 hrs of the MT, and the OGTT differed systematically because a different potentiation factor was involved. In fact, potentiation was higher than average during meals (1.6±0.1 fold during the first meal), and had a different time-course in the MT and OGTT. However, if potentiation was accounted for, the 24-hr and 2-hr MT and the OGTT yielded similar dose-responses, and most ß-cell function parameters were intercorrelated (r=0.50-0.86, p<0.05 or less). The potentiation factor was found to be related to plasma glucose-dependent insulin releasing polypeptide (GIP) concentrations (r=0.49, p<0.0001). Among ß-cell function parameters, only insulin secretion at 5 mM glucose from MT correlated inversely with insulin sensitivity (24-hr MT: r=-0.74, p<0.001; 2-hr MT: r=-0.52, p<0.05), whereas the dose-response slope and the OGTT parameters did not. In another 9 subjects, reproducibility of model parameters was evaluated from repeated MT's. Coefficients of variation were generally ~20%, but the derivative component was less reproducible. We conclude that our model for the multiple MT yields useful information on ß-cell function, particularly with regard to the role of potentiation. With cautious interpretation, a 2-hr MT or a standard OGTT can be used as surrogates of 24-hr tests in assessing spontaneous ß-cell function.
This article has been cited by other articles:
|
|
 |
|
  S. Bonuccelli, E. Muscelli, A. Gastaldelli, E. Barsotti, B. D. Astiarraga, J. J. Holst, A. Mari, and E. Ferrannini Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms Am J Physiol Endocrinol Metab, August 1, 2009; 297(2): E532 - E537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E Tushuizen, M. C Bunck, P. J W Pouwels, S. Bontemps, A. Mari, and M. Diamant Lack of association of liver fat with model parameters of {beta}-cell function in men with impaired glucose tolerance and type 2 diabetes Eur. J. Endocrinol., September 1, 2008; 159(3): 251 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Mingrone, M. Manco, M. E. Valera Mora, C. Guidone, A. Iaconelli, D. Gniuli, L. Leccesi, C. Chiellini, and G. Ghirlanda Influence of Maternal Obesity on Insulin Sensitivity and Secretion in Offspring Diabetes Care, September 1, 2008; 31(9): 1872 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Muscelli, A. Mari, A. Casolaro, S. Camastra, G. Seghieri, A. Gastaldelli, J. J. Holst, and E. Ferrannini Separate Impact of Obesity and Glucose Tolerance on the Incretin Effect in Normal Subjects and Type 2 Diabetic Patients Diabetes, May 1, 2008; 57(5): 1340 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pascoe, A. Tura, S. K. Patel, I. M. Ibrahim, E. Ferrannini, E. Zeggini, M. N. Weedon, A. Mari, A. T. Hattersley, M. I. McCarthy, et al. Common Variants of the Novel Type 2 Diabetes Genes CDKAL1 and HHEX/IDE Are Associated With Decreased Pancreatic {beta}-Cell Function Diabetes, December 1, 2007; 56(12): 3101 - 3104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Tushuizen, M. C. Bunck, P. J. Pouwels, S. Bontemps, J. H. T. van Waesberghe, R. K. Schindhelm, A. Mari, R. J. Heine, and M. Diamant Pancreatic Fat Content and {beta}-Cell Function in Men With and Without Type 2 Diabetes Diabetes Care, November 1, 2007; 30(11): 2916 - 2921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Holst The Physiology of Glucagon-like Peptide 1 Physiol Rev, October 1, 2007; 87(4): 1409 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mari, K. Degn, B. Brock, J. Rungby, E. Ferrannini, and O. Schmitz Effects of the Long-Acting Human Glucagon-Like Peptide-1 Analog Liraglutide on {beta}-Cell Function in Normal Living Conditions Diabetes Care, August 1, 2007; 30(8): 2032 - 2033. [Full Text] [PDF]
|
|
|
|
|
|
C. Cobelli, G. M. Toffolo, C. D. Man, M. Campioni, P. Denti, A. Caumo, P. Butler, and R. Rizza Assessment of beta-cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E1 - E15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Lauster, T. P. McKaveney, and S. V. Muench Vildagliptin: A novel oral therapy for type 2 diabetes mellitus Am. J. Health Syst. Pharm., June 15, 2007; 64(12): 1265 - 1273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Salinari, A. Bertuzzi, M. Manco, and G. Mingrone NEFA-glucose comodulation model of beta-cell insulin secretion in 24-h multiple-meal test Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1890 - E1898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gastaldelli, E. Ferrannini, Y. Miyazaki, M. Matsuda, A. Mari, and R. A. DeFronzo Thiazolidinediones improve beta-cell function in type 2 diabetic patients Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E871 - E883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Campioni, G. Toffolo, L. T. Shuster, F. J. Service, R. A. Rizza, and C. Cobelli Incretin effect potentiates beta-cell responsivity to glucose as well as to its rate of change: OGTT and matched intravenous study Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E54 - E60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Muscelli, A. Mari, A. Natali, B. D. Astiarraga, S. Camastra, S. Frascerra, J. J. Holst, and E. Ferrannini Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1144 - E1150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Panteleon, M. Loutseiko, G. M. Steil, and K. Rebrin Evaluation of the effect of gain on the meal response of an automated closed-loop insulin delivery system. Diabetes, July 1, 2006; 55(7): 1995 - 2000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Guidone, M. Manco, E. Valera-Mora, A. Iaconelli, D. Gniuli, A. Mari, G. Nanni, M. Castagneto, M. Calvani, and G. Mingrone Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery. Diabetes, July 1, 2006; 55(7): 2025 - 2031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Camastra, M. Manco, A. Mari, S. Baldi, A. Gastaldelli, A. V. Greco, G. Mingrone, and E. Ferrannini {beta}-Cell Function in Morbidly Obese Subjects During Free Living: Long-Term Effects of Weight Loss Diabetes, August 1, 2005; 54(8): 2382 - 2389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ahren, R. Gomis, E. Standl, D. Mills, and A. Schweizer Twelve- and 52-Week Efficacy of the Dipeptidyl Peptidase IV Inhibitor LAF237 in Metformin-Treated Patients With Type 2 Diabetes Diabetes Care, December 1, 2004; 27(12): 2874 - 2880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ferrannini, S. Camastra, A. Gastaldelli, A. Maria Sironi, A. Natali, E. Muscelli, G. Mingrone, and A. Mari Beta-Cell Function in Obesity: Effects of Weight Loss Diabetes, December 1, 2004; 53(suppl_3): S26 - S33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Sironi, A. Gastaldelli, A. Mari, D. Ciociaro, V. Postano, E. Buzzigoli, S. Ghione, S. Turchi, M. Lombardi, and E. Ferrannini Visceral Fat in Hypertension: Influence on Insulin Resistance and {beta}-Cell Function Hypertension, August 1, 2004; 44(2): 127 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ferrannini, M. Nannipieri, K. Williams, C. Gonzales, S. M. Haffner, and M. P. Stern Mode of Onset of Type 2 Diabetes from Normal or Impaired Glucose Tolerance Diabetes, January 1, 2004; 53(1): 160 - 165. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
