Elevated glucagon-like peptide-1-(7-36)-amide, but not glucose, associated with hyperinsulinemic compensation for fat feeding.
We previously developed a canine model of central obesity and insulin resistance by supplementing the normal chow diet with 2 g cooked bacon grease/kg body weight. Dogs fed this fatty diet maintained glucose tolerance with compensatory hyperinsulinemia. The signal(s) responsible for this up-regulation of plasma insulin is unknown. We hypothesized that meal-derived factors such as glucose, fatty acids, or incretin hormones may signal beta-cell compensation in the fat-fed dog. We fed the same fat-supplemented diet for 12 wk to six dogs and compared metabolic responses with seven control dogs fed a normal diet. Fasting and stimulated fatty acid and glucose-dependent insulinotropic peptide concentrations were not increased by fat feeding, whereas glucose was paradoxically decreased, ruling out those three factors as signals for compensatory hyperinsulinemia. Fasting plasma glucagon-like peptide-1 (GLP-1) concentration was 2.5-fold higher in the fat-fed animals, compared with controls, and 3.4-fold higher after a mixed meal. Additionally, expression of the GLP-1 receptor in whole pancreas was increased 2.3-fold in the fat-fed dogs. The increase in both circulating GLP-1 and its target receptor may have increased beta-cell responsiveness to lower glucose. Glucose is not the primary cause of hyperinsulinemia in the fat-fed dog. Corequisite meal-related signals may be permissive for development of hyperinsulinemia.
van Citters
Gregg W
GW
Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, 1333 San Pablo Street, Los Angeles, CA 90089-9142, USA.
Kabir
Morvarid
M
Kim
Stella P
SP
Mittelman
Steven D
SD
Dea
Melvin K
MK
Brubaker
Patricia L
PL
Bergman
Richard N
RN
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015152:Blotting, Northern; D004041:Dietary Fats / Q000008:administration & dosage*; D004285:Dogs; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015870:Gene Expression; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006946:Hyperinsulinism / Q000097:blood* / Q000209:etiology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects / Q000503:physiopathology; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D009765:Obesity / Q000097:blood; D010446:Peptide Fragments / Q000097:blood*; D018027:Receptors, Glucagon / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose