Role of the Kidney in T2DM Worldwide Diabetes（二型糖尿病肾脏在全球糖尿病的作用）.ppt

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2017-09-02 发布于浙江
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Role of the Kidney in T2DM Worldwide Diabetes（二型糖尿病肾脏在全球糖尿病的作用）.ppt

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Role of the Kidney in T2DM Worldwide Diabetes（二型糖尿病肾脏在全球糖尿病的作用）

* * By increasing glucosuria, SGLT2 inhibition reduces plasma glucose levels toward the normal level of 5 mmol/L (90 mg/dL). With the reduction in glucotoxicity, insulin secretion improves and insulin sensitivity is enhanced. In turn, these decrease hepatic glucose output. Evidence supporting these actions is described in the following slides. * * The major role of the kidney in human physiology is to maintain intravascular volume and an acid-based electrolyte balance. Approximately 180 L of plasma per day pass through the kidney’s glomerular filtration system, wherein minerals such as sodium, potassium, and chloride are absorbed and returned to the bloodstream rather than passed out in the urine. Glucose is also filtered in this manner in order to retain energy essential for physiologic functioning between meals. With a daily glomerular filtration rate of 180 L, approximately 162 g of glucose must be reabsorbed each day to maintain a plasma glucose concentration of 5.6 mmol/L (101 mg/dL). As shown on the slide, reabsorption of glucose occurs mainly in the proximal tubule and is mediated by 2 different transport proteins, SGLT1 and SGLT2. SGLT1, which occurs in the straight section of the tubule (S3), is responsible for approximately 10% of glucose reabsorption in the kidney. The other 90% is mediated by SGLT2, which occurs in the convoluted section on the tubule (S1). Wright EM, Hirayama BA, Loo DF. Active sugar transport in health and disease. J Intern Med. 2007;261:32-43. * This slide describes the differences between the 2 sodium-glucose transport proteins. SGLT1 is a high-affinity, low-capacity transport protein that resides in both the gut and the proximal tubule in the kidney. It plays a role in both dietary absorption and renal reabsorption of glucose. Inhibition of SGLT1 can result in malabsorption of glucose and other nutrients from the intestine, leading to osmotic diarrhea. For example, in glucose-galactose malabsorption syndrome, mutations in the ge