| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-cell dysfunction in vivo in models of progressive -cell failure
Departments of 1Physiology and 2Medicine, University of Toronto, Toronto, Ontario, Canada; and 3Institute of Biomedical Engineering, National Research Council, Padua, Italy
Submitted 26 May 2006 ; accepted in final form 19 September 2006
We determined the effect of 48-h elevation of plasma free fatty acids (FFA) on insulin secretion during hyperglycemic clamps in control female Wistar rats (group a) and in the following female rat models of progressive 
-cell dysfunction: lean Zucker diabetic fatty (ZDF) rats, both wild-type (group b) and heterozygous for the fa mutation in the leptin receptor gene (group c); obese (fa/fa) Zucker rats (nonprediabetic; group d); obese prediabetic (fa/fa) ZDF rats (group e); and obese (fa/fa) diabetic ZDF rats (group f). FFA induced insulin resistance in all groups but increased C-peptide levels (index of absolute insulin secretion) only in obese prediabetic ZDF rats. Insulin secretion corrected for insulin sensitivity using a hyperbolic or power relationship (disposition index or compensation index, respectively, both indexes of -cell function) was decreased by FFA. The decrease was greater in normoglycemic heterozygous lean ZDF rats than in Wistar controls. In obese "prediabetic" ZDF rats with mild hyperglycemia, the FFA-induced decrease in -cell function was no greater than that in obese Zucker rats. However, in overtly diabetic obese ZDF rats, FFA further impaired -cell function. In conclusion, 1) the FFA-induced impairment in -cell function is accentuated in the presence of a single copy of a mutated leptin receptor gene, independent of hyperglycemia. 2) In prediabetic ZDF rats with mild hyperglycemia, lipotoxicity is not accentuated, as the -cell mounts a partial compensatory response for FFA-induced insulin resistance. 3) This compensation is lost in diabetic rats with more marked hyperglycemia and loss of glucose sensing.
free fatty acid; obesity; insulin secretion; hyperglycemic clamp; Zucker diabetic fatty rat
This article has been cited by other articles:
|
|
 |
|
  L. M. Lauffer, R. Iakoubov, and P. L. Brubaker GPR119 Is Essential for Oleoylethanolamide-Induced Glucagon-Like Peptide-1 Secretion From the Intestinal Enteroendocrine L-Cell Diabetes, May 1, 2009; 58(5): 1058 - 1066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Salgin, M. L. Marcovecchio, S. M. Humphreys, N. Hill, L. J. Chassin, D. J. Lunn, R. Hovorka, and D. B. Dunger Effects of prolonged fasting and sustained lipolysis on insulin secretion and insulin sensitivity in normal subjects Am J Physiol Endocrinol Metab, March 1, 2009; 296(3): E454 - E461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Hagman, M. G. Latour, S. K. Chakrabarti, G. Fontes, J. Amyot, C. Tremblay, M. Semache, J. A. Lausier, V. Roskens, R. G. Mirmira, et al. Cyclical and Alternating Infusions of Glucose and Intralipid in Rats Inhibit Insulin Gene Expression and Pdx-1 Binding in Islets Diabetes, February 1, 2008; 57(2): 424 - 431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Tang, P. Han, A. I. Oprescu, S. C. Lee, A. V. Gyulkhandanyan, G. N.Y. Chan, M. B. Wheeler, and A. Giacca Evidence for a Role of Superoxide Generation in Glucose-Induced {beta}-Cell Dysfunction In Vivo Diabetes, November 1, 2007; 56(11): 2722 - 2731. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
