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Disruption Of Circadian Eating Patterns And Intestinal Glucose Uptake In Obesity-Induced Diabetes
Hina Y. Bhutta, MD1,3, Tara Deelman, MD1,3, David B. Rhoads, MD2,3, Ali Tavakkolizadeh, MD1,3
1Brigham and Women's Hospital, Boston, MA; 2Massachusetts General Hospital, Boston, MA; 3Harvard Medical School, Boston, MA

Background: Shift work, an increasingly prevalent work pattern, leads to misaligned circadian cycles and food intake and is associated with diabetes and obesity. We proposed that such deregulation of food intake alters gut glucose sensing (via taste receptors, T1R2) and nutrient transport (via glucose transporter SGLT1) leading to metabolic disease, and studied circadian patterns of feeding and gut glucose absorption in a rodent model of disease (ZDF rats).
Methods: Obese and lean ZDF rats were acclimatized (n=24/group) with high carbohydrate diet. Daily weights and day:night food intake were recorded. Jejunal SGLT1 and T1R2 mRNA levels, and functional glucose uptake were assessed. HOMA-IR was calculated to assess glucose resistance. Statistical analyses included t-test and Cosinor.
Results: Obese rats ate more than leans. Both groups had a disrupted circadian pattern of food intake with loss of rhythmicity of SGLT1 function. HOMA-IR was higher in obese rats (Table 1). Elevated serum glucose was associated with increased jejunal SGLT1 but decreased T1R2 mRNA in obese rats compared to leans.
Conclusion: In obese and lean ZDF rats diurnal feeding pattern was dampened, with ablated rhythmicity of glucose absorption. Since only obese rats developed diabetes, loss of rhythmicity per se does not appear etiological. Elevated SGLT1 despite low T1R2 levels indicates inappropriate nutrient sensing in the jejunum of obese rats. Isolating this segment of bowel in gastric bypass may explain its anti-diabetic effects.
Table 1. Food consumption patterns during acclimation period, Glucose and Insulin levels at harvest, and jejunal mRNA levels of SGLT1 and T1R2 genes.


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