Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Dig Dis Sci. 2013 Jun;58(6):1537-45. doi: 10.1007/s10620-013-2669-y. Epub 2013 Apr 30.
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.
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.
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.
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.
肠道吸收能力呈现与进食模式同步的昼夜节律。破坏这些协调的节律，例如轮班工作，可能导致代谢疾病。代谢疾病中尚未研究营养转运蛋白的昼夜节律表达。我们研究了肥胖糖尿病大鼠中肠转运体钠葡萄糖共转运蛋白 1（SGLT1）的昼夜节律。
我们比较了肥胖的 Zucker 糖尿病肥胖（ZDF）大鼠和瘦 ZDF 同窝仔鼠。评估了时间性进食模式，然后在 Zeitgeber（ZT，ZT0 = 上午 7:00）3、9 或 15 时收获大鼠，以测量胰岛素抵抗、SGLT1 表达和肠道葡萄糖吸收能力。测量 SGLT1 的调节剂（甜味受体 T1R2/3；时钟基因）以阐明潜在机制。
两组均表现出改变的昼夜性食物摄入。肥胖的 ZDF 大鼠失去了 SGLT1 mRNA 表达和功能活性的昼夜节律性。瘦的 ZDF 大鼠维持了 SGLT1 mRNA 表达的节律性，但功能性葡萄糖吸收的节律性减弱。两组的肠道时钟基因昼夜节律均得到维持。两组均未观察到肠道 GLUT2（葡萄糖转运蛋白）或 T1R2（甜味受体成分）mRNA 表达的节律性。总之，瘦和肥胖的 ZDF 大鼠表现出相似的昼夜性进食紊乱。瘦鼠出现葡萄糖不耐受，但只有肥胖大鼠进一步发展为糖尿病，并表现出 SGLT1 mRNA 表达和功能的昼夜节律紊乱。
我们的研究结果表明，昼夜节律性进食紊乱导致葡萄糖不耐受，但需要其他因素（遗传、营养感应/转运的变化）才能导致完全的糖尿病。
