Fasting and post-prandial splanchnic blood flow is reduced by a somatostatin analogue (octreotide) in man

Cooper, A. M.; Braatvedt, Geoffrey; Qamar, Mehwish; Brown, Heather J.; Thomas, David M.; Halliwell, Michael; Read, A. E.; Corrall, R. J. M.

doi:10.1042/cs0810169

Cited by 74 publications

(48 citation statements)

References 17 publications

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“…The uptake and metabolism of glucose by the liver after food intake is affected by the rate of glucose and hormone delivery, which in turn depends on portal vein blood flow during a meal (11). Portal venous blood flow increases by 20 to 80% 30 min after a meal, depending on the type of meal (liquid vs. solid), and remains elevated for 2 h after meal consumption (10,12,16,44). The main determinant of the postprandial increase in portal vein flow is the gastrointestinal hyperemic response that follows food digestion and absorption, which leads to a marked increase in blood outflow from extrahepatic splanchnic tissues to the portal system (38).…”

Section: E448 Metabolic Response To Different Meals In Baboonsmentioning

confidence: 99%

Metabolic response to high-carbohydrate and low-carbohydrate meals in a nonhuman primate model

Fabbrini

Higgins

Magkos

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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We established a model of chronic portal vein catheterization in an awake nonhuman primate to provide a comprehensive evaluation of the metabolic response to low-carbohydrate/high-fat (LCHF; 20% carbohydrate and 65% fat) and high-carbohydrate/low-fat (HCLF; 65% carbohydrate and 20% fat) meal ingestion. Each meal was given 1 wk apart to five young adult (7.8 Ϯ 1.3 yr old) male baboons. A [U-13 C]glucose tracer was added to the meal, and a [6,6-2 H2]glucose tracer was infused systemically to assess glucose kinetics. Plasma areas under the curve (AUCs) of glucose, insulin, and C-peptide in the femoral artery and of glucose and insulin in the portal vein were higher (P Յ 0.05) after ingestion of the HCLF compared with the LCHF meal. Compared with the LCHF meal, the rate of appearance of ingested glucose into the portal vein and the systemic circulation was greater after the HCLF meal (P Ͻ 0.05). Endogenous glucose production decreased by ϳ40% after ingestion of the HCLF meal but was not affected by the LCHF meal (P Ͻ 0.05). Portal vein blood flow increased (P Ͻ 0.001) to a similar extent after consumption of either meal. In conclusion, a LCHF diet causes minimal changes in the rate of glucose appearance in both portal and systemic circulations, does not affect the rate of endogenous glucose production, and causes minimal stimulation of C-peptide and insulin. These observations demonstrate that LCHF diets cause minimal perturbations in glucose homeostasis and pancreatic ␤-cell activity.stable isotope tracers; portal vein catheterization; ␤-cell function THE TYPICAL DIET IN THE US provides ϳ50% of ingested calories as carbohydrate, 35% as fat, and 15% as protein (4). However, data from several studies have shown that a low-carbohydrate diet containing 35-40% of calories as carbohydrate can have therapeutic effects in patients with type 2 diabetes by lowering plasma glucose, triglyceride, and very low-density lipoprotein (VLDL) cholesterol, by increasing plasma high-density lipoprotein (HDL) cholesterol concentrations, and by decreasing insulin requirements (17)(18)(19). In addition, low-carbohydrate diets are often used to help induce weight loss in obese people (15). Although the use of low-carbohydrate diets continues to be a popular dietary therapy, the metabolic response to highand low-carbohydrate meals has not been carefully evaluated.The metabolic response to a meal is carefully coordinated among several organ systems to prevent large excursions in plasma glucose concentration and to deliver ingested nutrients to appropriate tissues for storage or utilization. The normal regulation of postprandial plasma glucose involves an increase in insulin secretion from pancreatic ␤-cells into the portal vein, insulin-mediated suppression of endogenous (primarily hepatic) glucose production, and insulin-mediated stimulation of glucose uptake by peripheral tissues (primarily skeletal muscle). In fact, abnormalities in plasma glucose concentration after an oral glucose load is ingested are used as a clinical tool to diagnose...

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Section: E448 Metabolic Response To Different Meals In Baboonsmentioning

confidence: 99%

Metabolic response to high-carbohydrate and low-carbohydrate meals in a nonhuman primate model

Fabbrini

Higgins

Magkos

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…In addition, we concede that despite its benefits to inhibit endogenous insulin and glucagon secretion, octreotide may have independent effects on carbohydrate metabolism. 8 A third limitation is that there have been reports that general anesthesia can have direct effects on carbohydrate metabolism, specifically to raise glucose levels.…”

Section: Pharmacokinetics Of Glucagon Preparationsmentioning

confidence: 99%

Development of a Highly Stable, Nonaqueous Glucagon Formulation for Delivery via Infusion Pump Systems

Newswanger

Ammons

Phadnis

et al. 2014

J Diabetes Sci Technol

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SymposiumGlucagon is currently approved for the treatment of severe hypoglycemia.1,2 Because glucagon is not stable in aqueous solutions, these preparations are provided as lyophilized powders for reconstitution. Once reconstituted, these preparations begin to degrade and fibrillate rapidly and must be discarded if not used immediately. While suitable for treatment of severe hypoglycemia, these glucagon preparations are unstable and thus not suitable for development of additional indications including minidosing for mild to moderate hypoglycemia 3 and infusion pump applications. In particular, a stable glucagon suitable for use in infusion pump systems creates an opportunity for treatment of hypoglycemia under different conditions, including as a component of an artificial or "bionic" pancreas system. 4,5Despite a vigorous research effort, to date development of aqueous-based glucagon formulations (without reconstitution) has failed to produce any clinical candidates. We have developed a novel, nonaqueous glucagon formulation based on a biocompatible pharmaceutical solvent, dimethyl sulfoxide, which demonstrates excellent physical and chemical stability (up to 2 years at room temperature) 6 at relatively high concentrations.The solubility and stability of this formulation allow for development of a higher concentration formulation (5 mg/ml vs 1 mg/ml for the currently approved glucagon formulations) to facilitate administration from devices such as autoinjectors, pens, pumps, and so on. Furthermore, this glucagon formulation is in clinical development as a treatment for severe hypoglycemia 6 and moderate hypoglycemia and for management of blood glucose in pump applications.This article presents stability, compatibility, and preclinical data supporting progression of this formulation into clinical development. Background: Despite a vigorous research effort, to date, the development of systems that achieve glucagon stability in aqueous formulations (without reconstitution) has failed to produce any clinical candidates. We have developed a novel, nonaqueous glucagon formulation based on a biocompatible pharmaceutical solvent, dimethyl sulfoxide, which demonstrates excellent physical and chemical stability at relatively high concentrations and at high temperatures.

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“…Authors of these studies recommend trial of Octreotide in selected patients and continuation of therapy if there is a significant reduction in fistula output within 3 days [2]. Problems associated with the use of Octreotide include possible adverse effect on immune function [47] as well as decreased perfusion in the splanchnic and portal circulation, worsening cholestasis [48], not to mention cost.…”

Section: Electrolytes and Nutritionmentioning

confidence: 99%

Enterocutaneous Fistulas: A Look at Causes and Management

2014

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Despite advances in medical technology and surgical care, the management of enterocutaneous fistulas remains one of the most challenging problems faced by physicians. Success depends on an expert multidisciplinary team, access to long-term enteral and parenteral nutrition support, advanced wound care, optimal medical management and meticulous, methodical, surgical decision-making and technique. Management is complex and multiphasic. Improved survival rates for many morbid problems have resulted in a growing population of patients with increasingly complex fistulas. This article reviews the etiologies as well as classic and evolving management strategies for this problem.

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Fasting and post-prandial splanchnic blood flow is reduced by a somatostatin analogue (octreotide) in man

Cited by 74 publications

References 17 publications

Metabolic response to high-carbohydrate and low-carbohydrate meals in a nonhuman primate model

Metabolic response to high-carbohydrate and low-carbohydrate meals in a nonhuman primate model

Development of a Highly Stable, Nonaqueous Glucagon Formulation for Delivery via Infusion Pump Systems

Enterocutaneous Fistulas: A Look at Causes and Management

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