Increased dietary fat promotes islet amyloid formation and beta-cell secretory dysfunction
| Autor: | Hull, R. L., Andrikopoulos, S., Verchere, C. B., Vidal, J., Wang, F., Cnop, Miriam, Prigeon, R. L., Kahn, Steven E. |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Male
endocrine system Islets of Langerhans -- physiopathology endocrine system diseases Blood Glucose -- metabolism Somatostatin -- metabolism Body Weight Mice Transgenic Glucose Tolerance Test Glucose Intolerance -- blood Dietary Fats -- pharmacology Glucose Intolerance -- physiopathology Amyloid -- physiology Glucagon -- metabolism Mice Islets of Langerhans -- drug effects Islets of Langerhans -- secretion Amyloid -- genetics Animals Humans Médecine clinique [biologie clinique] Insulin -- analysis Pancreatic Polypeptide -- metabolism |
| Zdroj: | Diabetes, 52 |
| Popis: | Transgenic mice expressing the amyloidogenic human islet amyloid polypeptide (hIAPP) in their islet beta-cells are a model of islet amyloid formation as it occurs in type 2 diabetes. Our hIAPP transgenic mice developed islet amyloid when fed a breeder chow but not regular chow. Because the breeder chow contained increased amounts of fat, we hypothesized that increased dietary fat enhances islet amyloid formation. To test this hypothesis, we fed male hIAPP transgenic and nontransgenic control mice diets containing 15% (low fat), 30% (medium fat), or 45% (high fat) of calories derived from fat for 12 months, and we measured islet amyloid, islet endocrine cell composition, and beta-cell function. Increased dietary fat in hIAPP transgenic mice was associated with a dose-dependent increase in both the prevalence (percentage of islets containing amyloid deposits; 34 +/- 8, 45 +/- 8, and 58 +/- 10%, P < 0.05) and severity (percentage of islet area occupied by amyloid; 0.8 +/- 0.5, 1.0 +/- 0.5, and 4.6 +/- 2.5%, P = 0.05) of islet amyloid. In addition, in these hIAPP transgenic mice, there was a dose-dependent decrease in the proportion of islet area comprising beta-cells, with no significant change in islet size. In contrast, nontransgenic mice adapted to diet-induced obesity by increasing their islet size more than twofold. Increased dietary fat was associated with impaired insulin secretion in hIAPP transgenic (P = 0.05) but not nontransgenic mice. In summary, dietary fat enhances both the prevalence and severity of islet amyloid and leads to beta-cell loss and impaired insulin secretion. Because both morphologic and functional defects are present in hIAPP transgenic mice, this would suggest that the effect of dietary fat to enhance islet amyloid formation might play a role in the pathogenesis of the islet lesion of type 2 diabetes in humans. Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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