Porcine Model of Diabetic Dyslipidemia: Insulin and Feed Algorithms for Mimicking Diabetes Mellitus in Humans
Abstract:A weakness of many animal models of diabetes mellitus is the failure to use insulin therapy, which typically results in severe body wasting. Data collected from such studies must be interpreted cautiously to separate the effects of hyperglycemia from those of starvation. We provide several algorithms that were used by us in two longterm (20-week) experiments in which hyperglycemia (300 to 400 mg/dl), dyslipidemia (cholesterol [280 to 405 mg/dl] and triglycerides [55 to 106 mg/dl] concentrations), and positive energy balance were maintained in swine. Yucatan miniature swine groups included control, alloxan-induced diabetes mellitus, diabetes mellitus plus diet-induced dyslipidemia, and exercise-trained diabetic dyslipidemic pigs. The algorithms were developed for the porcine model because of several similarities to humans, including: cardiac anatomy and physiology, propensity for sedentary behavior, and metabolism of dietary carbohydrates and lipids. Acute toxic effects of alloxan (hypoglycemia, hyperglycemia, nephrotoxicosis) were minimized by preventive fluid loading and by use of algorithms in which insulin, food, and fluid therapy were administered. Long-term insulin and food maintenance algorithms elicited normal body weight gain in all three diabetic groups (lean experiment) and threefold greater body weight gain in pigs of an obesity experiment. Exercise-trained pigs of both experiments manifested significantly increased work performance and did not experience medical complications. We conclude that these algorithms can be used in swine, or similar algorithms can be developed for other animal species to maintain hyperglycemia and/or dyslipidemia, while avoiding diabetes-induced wasting. Importantly, animal models of diabetes mellitus that maintain positive energy balance and poor glycemic control provide a marked improvement over other models by more closely mimicking the human presentation of diabetes mellitus.
Document Type: Research Article
Affiliations: 1: Departments of Physiology, University of Missouri, Columbia, Missouri 65212 2: School of Medicine, Dalton Cardiovascular Research Center, Diabetes and Cardiovascular Biology Program, University of Missouri, Columbia, Missouri 65212 3: Departments of Physiology, Internal Medicine, Diabetes and Cardiovascular Biology Program, University of Missouri, Columbia, Missouri 65212, Supported by the National Institutes of Health grants RR13223 and HL62552 to MS and HL10474 to EAM
Publication date: February 1, 2003
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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