title: Disrupted circadian rhythmicity of the intestinal glucose transporter SGLT1 in Zucker diabetic fatty rats.
abstract: BACKGROUND
  Intestinal absorptive capacity shows a circadian rhythm synchronized with eating patterns. Disrupting these coordinated rhythms, e.g., with shift work, may contribute to metabolic disease. Circadian expression of nutrient transporters has not been studied in metabolic disease. We studied the circadian rhythm of intestinal transporter sodium glucose co-transporter type 1 (SGLT1) in an obese diabetic rat.
  
  
  METHODS
  We compared obese Zucker diabetic fatty (ZDF) rats to lean ZDF littermates. Temporal feeding patterns were assessed, then rats were harvested at Zeitgeber (ZT, ZT0 = 7:00 a.m.) 3, 9, or 15 to measure insulin resistance, SGLT1 expression and intestinal glucose absorption capacity. Regulators of SGLT1 (sweet taste receptor T1R2/3; clock genes) were measured to elucidate underlying mechanisms.
  
  
  RESULTS
  Both groups exhibited altered circadian food intake. Obese ZDF rats lost circadian rhythmicity of SGLT1 mRNA expression and functional activity. Lean ZDF rats maintained rhythmicity of SGLT1 mRNA expression but that of functional glucose absorption was blunted. Circadian rhythms of intestinal clock genes were maintained in both groups. Neither group had discernible rhythms of intestinal GLUT2 (glucose transporter) or T1R2 (sweet taste receptor component) mRNA expression. In summary, lean and obese ZDF rats exhibited similar disruptions in circadian feeding. Glucose intolerance was evident in lean rats, but only obese rats further developed diabetes and exhibited disrupted circadian rhythmicity of both SGLT1 mRNA expression and function.
  
  
  CONCLUSIONS
  Our findings suggest that disrupted circadian feeding rhythms contribute to glucose intolerance, but additional factors (genetics, changes in nutrient sensing/transport) are needed to lead to full diabetes.
authors: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. hbhutta@partners.org
authors: Hina Y
authors: HY
authors: Bhutta
authors: Tara E
authors: TE
authors: Deelman
authors: Stanley W
authors: SW
authors: Ashley
authors: David B
authors: DB
authors: Rhoads
authors: Ali
authors: A
authors: Tavakkoli
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D021081:Chronobiology Disorders / Q000150:complications* / Q000378:metabolism; D002940:Circadian Rhythm; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology; D018149:Glucose Intolerance / Q000209:etiology* / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000150:complications / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D043562:Receptors, G-Protein-Coupled; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; C431926:taste receptors, type 1
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