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Objective-We set out to examine the short-term regulation of the intestinal sodium/glucose cotransporter SGLT1 by its substrate glucose and sweet taste analogs.Summary Background Data-Intestinal SGLT1 is a putative target for antidiabetic therapy; however, its physiological regulation is incompletely understood, limiting its application as a pharmacological target. While it is clearly regulated by dietary composition over a period of days, its short-term regulation by nutrients is unknown.Methods-Sprague-Dawley rats were anesthetized, and the duodenum cannulated. D-glucose, Dfructose, saccharin, D-mannitol, and water were infused for 3 hours, before harvest of proximal jejunum for SGLT1 analysis with Western blotting and quantitative polymerase chain reaction. In further experiments, the receptor region was identified by D-glucose infusion of isolated regions. Lastly, the vagus was de-afferented with capsaicin, and 5HT3-receptor activation of vagal afferents inhibited using ondansetron, before repeating experiments using water or D-glucose infusion.

Stearns AT, Balakrishnan A, Tavakkolizadeh A. Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport. Am J Physiol Gastrointest Liver Physiol 297: G950-G957, 2009. First published September 3, 2009 doi:10.1152/ajpgi.00253.2009.-Roux-en-Y gastric bypass (RYGB) has become the gold-standard bariatric procedure, partly because of the rapid resolution of accompanying diabetes. There is increasing evidence this is mediated by duodenal exclusion. We hypothesize that duodenal exclusion suppresses intestinal Na ϩ /glucose cotransporter SGLT1-mediated glucose transport, improving glucose handling, and aimed to test this in a rodent RYGB model. Sprague-Dawley rats underwent sham procedure or duodenal exclusion by RYGB (10 cm Roux, 16 cm biliopancreatic limbs). Animals were maintained for 3 wk on a Western diet, before harvest at 10 AM, 4 PM, and 10 PM. Sections were taken from each limb for hematoxylin and eosin staining, and morphological assessment was performed. Functional glucose uptake studies, along with Western blotting and quantitative PCR, were performed on Roux limb. Histology showed morphometric changes in Roux and common limbs, with increase in villus height and crypt depth compared with BP and sham jejunum. Despite this, glucose transport was reduced by up to 68% (P Ͻ 0.001) in the Roux limb compared with sham jejunum. Normal diurnal rhythms in glucose uptake were ablated. This occurred at a posttranscriptional level, with little change in message but appearance of different weight species of Sglt1 on Western blotting. We have shown duodenal exclusion significantly influences both intestinal structure and glucose transport function, with glucose absorptive capacity reduced after RYGB. This provides a novel mechanistic explanation for some of the antidiabetic effects of RYGB. bariatric surgery; diabetes; sglt1 OBESITY, TOGETHER WITH ASSOCIATED Type 2 diabetes mellitus (T2DM), has become a surgical disease (29). Bariatric surgery now represents the first-line treatment for morbid obesity, leading to resolution of obesity-related comorbidities such hypertension, sleep apnea, and T2DM and consequently improved life expectancy (1, 9, 35).Roux-en-Y gastric bypass (RYGB) is regarded as the goldstandard therapy for weight loss, with 60 -70% excess weight loss at two years (7). An important observation is the rapid associated resolution of T2DM, achieved prior to any significant weight loss; 84% of all patients had complete remission of T2DM, often within days after surgery (7). These impressive results have led many to regard RYGB as a metabolic operation. Unfortunately, 70% of T2DM patients do not fulfill the weight criteria to be eligible for bariatric surgery. Although there has been debate about the role of this procedure in T2DM in less obese patients, the invasive nature of the procedure has prevented widespread acceptance (10,23,34).Unfortunately, the mechanisms underlying diabetes resolution in RYGB remain unclear, limiting development of less invasive alternatives. A major feature of T...