Endocrine Abstracts (2004) 7 P38

Reduced insulin content and secretory capacity in the adult offspring of rats exposed to a high fat diet in pregnancy

SJ Persaud1, PD Taylor2, L Poston2, H Asare-Anane1, CJ Burns1 & PM Jones1

1Centre for Reproduction, Endocrinology and Diabetes, King's College London, UK; 2Diabetes and Maternal and Fetal Research Unit, King's College London, UK.

Objective: To investigate pancreatic beta cell morphology and function in rat adult offspring of dams fed a high fat diet in pregnancy.

Methods: Female Sprague Dawley rats were fed either a control breeding diet (4% fat) or a high fat diet (20% animal fat) balanced for vitamins and nutrients. Experimental diets were fed for 10 days prior to mating, throughout pregnancy and weaning. Weaned pups were fed standard low fat chow throughout adult life. The time-course of insulin secretion from isolated islets was determined by radioimmunoassay of perifusion samples. Islet insulin content was also measured by radioimmunoassay and preproinsulin mRNA levels were quantified by real-time RT-PCR. Electron micrographs of isolated pancreata were prepared for assessment of islet cell ultrastructure.

Results: Perifusion experiments indicated that glucose-stimulated insulin secretion was significantly reduced in islets isolated from the adult offspring of high fat dams (OHF). Both the initial peak phase and the sustained phase insulin secretion in response to 20mM glucose were significantly reduced in the experimental group (control: 438.8 plus/minus 46.3 pg/islet/20 min; OHF: 321.1 plus/minus 26.0, n=4, P<0.05). Islet insulin content was significantly reduced in the OHF rats (control: 26.9 plus/minus 2.6 ng/islet; OHF: 16.2 plus/minus 2.0, n=8-9, P<0.05). Preproinsulin mRNA levels were also significantly reduced in the experimental group (control: 35.6 plus/minus 8.3 pg/1000 copies actin; OHF: 9.4 plus/minus 2.1, n=3-4, P<0.05). Electron micrographs indicated altered ultrastructure of the beta cell secretory granules: OHF rat islets contained beta cell secretory granules with enlarged electron translucent halos, but with electron dense cores that were similar to control beta cells. The alpha cell secretory granules were not altered in the OHF islets.

Conclusions: These results are consistent with a high fat maternal diet permanently programming structural and functional abnormality of islet beta cells in the adult offspring of fat fed pregnant rats.

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