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With Type 2 human diabetes climbing at alarming rates in the UnitedStates, researchers are seeking treatments for the disease, whichhas been linked to obesity and poor diet. Now biologists at Southern Methodist University, Dallas, reportthey have developed a new tool that will help researchers betterunderstand this deadly disease. By manipulating the diets of healthy adult fruit flies, theresearchers developed flies that are insulin-resistant, a hallmarkof Type 2 diabetes. Until now, researchers largely have relied on rats, mice and otheranimals as model systems for exploring the metabolic and geneticchanges that take place in diabetics. The fruit fly Drosophila melanogaster has been widely deployed in labs to investigate a wide range ofhuman diseases, from Alzheimer's to cancer. But the scientificliterature hasn't documented use of the adult fruit fly forstudying the metabolic disruptions that are the hallmark of Type 2diabetes. The fruit fly's advantages include its low cost and avery short lifespan, both of which enable scientists to undertakerapid screenings in their search for new genetic and drugtreatments. The insulin-resistant fruit fly was developed in the lab of SMUbiologist Johannes H. Bauer, principal investigator for the study.It was accomplished by feeding fruit flies a diet high innutrients, said Bauer, an assistant professor in SMU's Departmentof Biological Sciences. That process mimics one of the ways insulinresistance develops in humans -- overeating to the point ofobesity. The lab's insulin-resistant fruit flies now can serve as a highlyrelevant and efficient model for studying Type 2 diabetes. "We learned that by manipulating the nutrients of fruit flies,we can make them insulin resistant," Bauer said. "Withthis insulin-resistant model we can now go in with pinpointprecision and study the molecular mechanisms of insulin resistance,as well as drug treatments for the condition, as well as how totreat obesity, how to block insulin resistance and how metabolicchanges from a specific diet develop. The possibilities areendless." The researchers reported their findings in the article"Development of diet-induced insulin resistance in adult Drosophila melanogaster ," published in Biochimica et Biophysica Acta -- MolecularBasis of Disease. Two overfeeding diets, carb and protein, both result in insulinresistance Insulin, produced by the pancreas, is the hormone that tells ourcells to absorb glucose, a necessary sugar molecule that providesour body, particularly the brain, with the energy to function, makerepairs, move and grow. In Type 2 diabetes, a person is insulin-resistant because his orher cells fail to respond to insulin's signal to absorb glucose.The disregulation of glucose upsets the body's delicate internalequilibrium, causing massive disruptions in normal cellularprocesses. These interruptions manifest in multiple diseasesymptoms, making Type 2 diabetes difficult to characterize, treatand cure. To provide a good base model organism to study aspects of thiscomplex disease, researchers in the Bauer lab wanted to determinewhether flies develop diabetes-like metabolic changes when feddifferent diets. The researchers developed the insulin-resistantflies in two different ways: One group of fruit flies was overfed acarbohydrate-loaded diet; a second group of flies was overfed aprotein-loaded diet. In both cases, the disruption had a profoundlydetrimental effect on the flies' health and physiology. SMU biologist Siti Nur Sarah Morris, lead author on the study, saidthe results the researchers observed were both expected andunexpected. The researchers expected the flies to gain weight,which they did. Carb-loaded flies gained excessive weight and gotfat, just like humans who overeat sweets, french fries, pasta andice cream. Protein-loaded flies also gained weight, but uponextreme overfeeding they lost weight, just like humans who followthe popular Atkins Diet, a weight loss program in whichparticipants eat only meat, seafood and eggs. The researchers expected the carb-loaded fruit flies to developinsulin resistance, which they did. In a surprising result, however, the fruit flies that overateprotein also developed insulin resistance, but at a quicker andmore severe rate. "Carb-loaded flies gain weight. Protein-loaded flies gain andthen lose weight. So the two diets have exactly opposite effects onmetabolism," Bauer said. "But too much of either one ofthem causes insulin resistance. That surprised us." Overfed flies had shortened lifespans, differences in fertility In other findings, carb-loaded flies experienced a profound declinein egg-laying, a measurement of fertility. In contrast,protein-loaded flies first experienced increased egg-laying, butthe extreme diet led to decreased egg laying. Both diets led toshortened longevity, the scientists reported. "The high-protein flies looked frail and unhealthy. They movedless, almost as if sedated," Morris said. "The fatterflies on the high-carb diet had massively decreased fertility; theyflew less but still tried to move." While both diets resulted in insulin resistance, differences wereremarkable. "The carb data imply a linear relationship between carb levelsand health. The more carbs, the more weight, the more sugar storageand fat, the more insulin resistance and the less fertility,"Bauer said. "But with protein, this relationship becomesparabolic, meaning all readouts go up, then come down again. Thedecreased storage we liken to a catabolic state that is primarilydestructive for the body's optimum metabolic functioning, such asthe ketosis typically seen in people eating Atkins-typediets." Besides Morris and Bauer, other authors on the study were SMUstudents Claire Coogan, Khalil Chamseddin and Santharam Kolli.Other co-authors, from Pennington Biomedical Research Center, BatonRouge, La., are Jeffrey N. Keller, director, Institute of DementiaResearch & Prevention, and Sun Ok Fernandez-Kim. The researchwas funded by the National Institute on Aging. We are high quality suppliers, our products such as Metal Roll Forming Machine Manufacturer , Stud Roll Forming Machine for oversee buyer. To know more, please visits Pipe Forming Machine.
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