Effects of duodenal and distal ileal infusions of glucose and oleic acid on meal patterns in rats

Woltman, Todd; Reidelberger, Roger D.

doi:10.1152/ajpregu.1995.269.1.r7

Cited by 35 publications

(53 citation statements)

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“…In contrast, the RYGB, by suppressing intestinal glucose absorption would slow glucose uptake, blunting postprandial portal glycemic excursions. Furthermore, this would enhance ileal delivery of glucose, with consequential effects on ileal gut peptide hormone secretion and satiety ("hind gut" theory) (27,42). Future studies in disease models will therefore need to evaluate hormonal changes that may occur with this surgery and contribute to the therapeutic benefit.…”

Section: Discussionmentioning

confidence: 99%

Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport

Stearns

Balakrishnan

Tavakkolizadeh

2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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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...

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Section: Discussionmentioning

confidence: 99%

Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport

Stearns

Balakrishnan

Tavakkolizadeh

2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The decreased function of Cys92 may well move fat digestion farther down the small intestine than normally occurs. Delayed digestion and release of fatty acids farther down the intestine may alter food intake through a mechanism that might include the action of gut hormones (19)(20)(21)(22)(23)(24)(25)(26). In the case of Cys92 colipase, the decreased function may be enough to limit the satiety response originating in the upper intestine by producing lower concentrations of fatty acids.…”

Section: Discussionmentioning

confidence: 99%

A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides

D'Silva

Xiao

Lowe

2007

Journal of Lipid Research

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Type 2 diabetes mellitus is a multifactorial and polygenic disorder with increasing prevalence. Recently, a polymorphism in the gene encoding procolipase, a cysteine for arginine substitution at position 92, was associated with type 2 diabetes in two human populations. Because procolipase plays a critical role in dietary fat metabolism, polymorphisms that affect the function of procolipase could influence the development of type 2 diabetes. We hypothesized that the Arg92Cys polymorphism has functional consequences. To test our hypothesis, we expressed recombinant cysteine 92 (Cys92) procolipase in a yeast expression system and compared the function and stability of purified Cys92 with that of the more common arginine 92 (Arg92) procolipase. Cys92 fully restored the activity of bile-salt inhibited lipase with short-and medium-chain triglycerides but only had 50% of Arg92 function with long-chain triglycerides. After storage at 4jC, Cys92 lost the ability to restore pancreatic triglyceride lipase activity with medium-and long-chain triglycerides. The loss of function correlated with the inability of Cys92 to anchor lipase on an emulsion surface and oxidation of the cysteine. No detectable degradation or intramolecular disulfide formation occurred in Cys92 after storage. Our findings demonstrate that the Arg92Cys polymorphism decreases the function of Cys92 colipase. This change may contribute to the development of type 2 diabetes.-D'Silva, S., X. Xiao, and M. E. Lowe. A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides. Pancreatic colipase has a central role in dietary fat digestion (1). Dietary fats, of which triglycerides constitute .95%, provide 30-40% of the total caloric intake in the Western diet. Before uptake into the enterocyte and transport into the circulation, fatty acids must be released from triglycerides by lipases. Fatty acid release begins with lipolysis in the stomach and proceeds in the upper duodenum, where the majority of fatty acids are released by pancreatic triglyceride lipase (PTL). Many other constituents found in intestinal chyme, such as bile salts and phospholipids, inhibit PTL. In vitro, colipase restores activity to PTL in the presence of these inhibitors (2). In vivo, reports of colipase deficiency in humans and in mice support the role of colipase in dietary fat digestion. Both colipasedeficient humans and mice have fat maldigestion and maladsorption (1, 3).The mRNA for human colipase encodes preprocolipase, a 112 amino acid protein with a molecular mass of 11.6 kDa (4). The first 17 amino acids constitute a signal peptide. Removal of the signal peptide results in the formation of procolipase. Procolipase is the secreted form, which is converted to colipase by proteolytic cleavage, probably by trypsin, of an N-terminal pentapeptide. The peptide, called enterostatin, has been implicated in the control of voluntary fat intake (5). Berger et al. (6) proposed that enterostatin restricts fat int...

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“…Similarly, knockout of the SGLT1 regulatory subunit protein RS1 in mice leads to both SGLT1 overexpression and severe obesity (27). Therapy aimed at modulating SGLT1 expression may therefore have clinical benefits in diabetes and obesity through slowing of glucose absorption in a manner similar to amylase inhibitors (5) and through increased ileal glucose delivery (38). SGLT1 expression is regulated by several inputs, including diet composition (11) and the timing of food intake (28).…”

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confidence: 99%

Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na⁺/glucose cotransporter SGLT1

Stearns¹,

Balakrishnan²,

Rounds³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Stearns AT, Balakrishnan A, Rounds J, Rhoads DB, Ashley SW, Tavakkolizadeh A. Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na ϩ /glucose cotransporter SGLT1. Am J Physiol Gastrointest Liver Physiol 294: G1078-G1083, 2008. First published February 28, 2008 doi:10.1152/ajpgi.00591.2007.-Introduction: the intestinal Na ϩ /glucose cotransporter (SGLT1) displays rapid anticipatory diurnal rhythms in mRNA and protein expression. The vagus nerve has been implicated in the entrainment of some transporters. We aimed to clarify the influence of the vagus nerve on the diurnal entrainment pathway for SGLT1 and examine the role of vagal afferent fibers. Methods: male Sprague-Dawley rats were randomized to three groups, total subdiaphragmatic vagotomy, selective deafferentation of the vagus with capsaicin, or sham laparotomy. Postoperatively, animals were maintained in a 12-h light-dark cycle with food access limited to night. On the ninth postoperative day, animals were euthanized to harvest jejunal mucosa at 6-h intervals starting at 10 AM. Whole cell SGLT1 protein was measured by semiquantitative densitometry of immunoblots. Sglt1 and regulatory subunit RS1 mRNA was assessed by quantitative PCR. Fluorogold tracer technique was used to confirm adequacy of the vagotomy. Results: the diurnal rhythm in intestinal SGLT1, with a 5.3-fold increase in Sglt1 mRNA at 4 PM, was preserved in both vagotomy and capsaicin groups. However, the rhythmicity in SGLT1 protein expression (2.3-fold peak at 10 PM; P ϭ 0.041) was abolished following either total vagotomy or deafferentation. Lack of change in RS1 mRNA suggests this is independent of the RS1 regulatory pathway. Conclusion: SGLT1 transcription is independent of the vagus. However, dissociation of the protein rhythm from the underlying mRNA signal by vagotomy suggests the vagus may be involved in posttranscriptional regulation of SGLT1 in an RS1 independent pathway. Disruption following afferent ablation by capsaicin suggests this limb is specifically necessary. glucose transport; vagus; vagotomy THE APICAL na ϩ /glucose cotransporter (SGLT1), localized on the brush-border membrane of small bowel enterocytes, is responsible for all secondary active absorption of glucose from the small bowel (14,19). Dysregulation of SGLT1 is increasingly recognized in type 2 diabetes mellitus, with expression increasing up to fourfold in both patients and animal models (4, 7-9). Similarly, knockout of the SGLT1 regulatory subunit protein RS1 in mice leads to both SGLT1 overexpression and severe obesity (27). Therapy aimed at modulating SGLT1 expression may therefore have clinical benefits in diabetes and obesity through slowing of glucose absorption in a manner similar to amylase inhibitors (5) and through increased ileal glucose delivery (38). SGLT1 expression is regulated by several inputs, including diet composition (11) and the timing of food intake (28). Despite significant progress in characterizing the physiological signaling mechanisms regulating SGL...

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Effects of duodenal and distal ileal infusions of glucose and oleic acid on meal patterns in rats

Cited by 35 publications

References 0 publications

Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport

Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport

A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides

Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na⁺/glucose cotransporter SGLT1

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Effects of duodenal and distal ileal infusions of glucose and oleic acid on meal patterns in rats

Cited by 35 publications

References 0 publications

Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport

Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport

A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides

Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na+/glucose cotransporter SGLT1

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Capsaicin-sensitive vagal afferents modulate posttranscriptional regulation of the rat Na⁺/glucose cotransporter SGLT1