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Mechanisms of Glucose Absorption in the Small Intestine in Health and Metabolic Diseases and Their Role in Appetite Regulation.
Gromova, LV, Fetissov, SO, Gruzdkov, AA
Nutrients. 2021;(7)
Abstract
The worldwide prevalence of metabolic diseases such as obesity, metabolic syndrome and type 2 diabetes shows an upward trend in recent decades. A characteristic feature of these diseases is hyperglycemia which can be associated with hyperphagia. Absorption of glucose in the small intestine physiologically contributes to the regulation of blood glucose levels, and hence, appears as a putative target for treatment of hyperglycemia. In fact, recent progress in understanding the molecular and cellular mechanisms of glucose absorption in the gut and its reabsorption in the kidney helped to develop a new strategy of diabetes treatment. Changes in blood glucose levels are also involved in regulation of appetite, suggesting that glucose absorption may be relevant to hyperphagia in metabolic diseases. In this review we discuss the mechanisms of glucose absorption in the small intestine in physiological conditions and their alterations in metabolic diseases as well as their relevance to the regulation of appetite. The key role of SGLT1 transporter in intestinal glucose absorption in both physiological conditions and in diabetes was clearly established. We conclude that although inhibition of small intestinal glucose absorption represents a valuable target for the treatment of hyperglycemia, it is not always suitable for the treatment of hyperphagia. In fact, independent regulation of glucose absorption and appetite requires a more complex approach for the treatment of metabolic diseases.
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Glutathione depleting drugs, antioxidants and intestinal calcium absorption.
Moine, L, Rivoira, M, Díaz de Barboza, G, Pérez, A, Tolosa de Talamoni, N
World journal of gastroenterology. 2018;(44):4979-4988
Abstract
Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2+ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca2+ absorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxidative/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca2+ transport or the paracellular Ca2+ route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca2+ pathway are decreased. The flavonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca2+ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca2+ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca2+ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety, pharmacokinetics and pharmacodynamics of them.
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3.
Absorption of Carotenoids and Mechanisms Involved in Their Health-Related Properties.
Cervantes-Paz, B, Victoria-Campos, CI, Ornelas-Paz, Jde J
Sub-cellular biochemistry. 2016;:415-54
Abstract
Carotenoids participate in the normal metabolism and function of the human body. They are involved in the prevention of several diseases, especially those related to the inflammation syndrome. Their main mechanisms of action are associated to their potent antioxidant activity and capacity to regulate the expression of specific genes and proteins. Recent findings suggest that carotenoid metabolites may explain several processes where the participation of their parent carotenoids was unclear. The health benefits of carotenoids strongly depend on their absorption and transformation during gastrointestinal digestion. The estimation of the 'bioaccessibility' of carotenoids through in vitro models have made possible the evaluation of the effect of a large number of factors on key stages of carotenoid digestion and intestinal absorption. The bioaccessibility of these compounds allows us to have a clear idea of their potential bioavailability, a term that implicitly involves the biological activity of these compounds.
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4.
Green tea influences intestinal assimilation of lipids in humans: a pilot study.
Lisowska, A, Stawińska-Witoszyńska, B, Bajerska, J, Krzyżanowska, P, Walkowiak, J
European review for medical and pharmacological sciences. 2015;(2):209-14
Abstract
OBJECTIVE Many data show that green tea (GT) consumption has a beneficial effect on human health, including antiinflammatory, antibacterial and anticarcinogenic activities. However, there are no data on the effect of long-term GT intake on lipid assimilation not related to luminal processes. Therefore, in the present study, we aimed to assess the impact of a three-month diet enriched in green tea extract (GTE) on lipid digestion and absorption in obese humans with metabolic syndrome. PATIENTS AND METHODS Eight obese subjects aged 56-65 years, for three months, consumed a daily portion of GTE enriched bread. 13C-labelled mixed triglyceride breath test (13C MTG-BT) was performed twice; once before and once after three months of GTE consumption. Cumulative percentage dose recovery (CPDR) was assumed to reflect digestion and absorption of lipids. RESULTS Energy and macronutrient intake was stable within the period study. No significant changes in basic anthropological parameters (body weight, BMI, WC, WHR), body fat content (expressed as absolute and relative values), as well as of energy expenditure in the course of the study were observed. Significant decrease in lipid digestion and absorption as assessed using the 13C MTG-BT was observed. CPDR was lower after GTE intake (median <1st-3rd quartile>: 20.8% <14.9-25.6> vs. 15.5 <12.3-20.5>; p < 0.009). CONCLUSIONS Long-term diet containing GTE decreases lipid assimilation, but probably without involvement of luminal effects. However, further studies are needed to confirm this hypothesis and to clarify underlying mechanism.
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5.
Growth hormone enhances fat-free mass and glutamine availability in patients with short-bowel syndrome: an ancillary double-blind, randomized crossover study.
Seguy, D, Darmaun, D, Duhamel, A, Thuillier, F, Cynober, L, Cortot, A, Gottrand, F, Messing, B
The American journal of clinical nutrition. 2014;(3):850-8
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Abstract
BACKGROUND Benefits of recombinant human growth hormone (rhGH) alone or combined with glutamine in patients with intestinal failure because of short-bowel syndrome remain controversial. OBJECTIVE We explored effects of rhGH on whole-body protein metabolism in patients with short-bowel syndrome with intestinal failure (SBS-IF) to gain insight into its mechanism of action. DESIGN Eight stable hyperphagic patients with severe SBS-IF received, in a double-blind, randomized crossover study, low-dose rhGH (0.05 mg · kg⁻¹ · d⁻¹) and a placebo for two 3-wk periods. Leucine and glutamine kinetics under fasting and fed conditions, fat-free mass (FFM), and serum insulin were determined on the final day of each treatment. RESULTS rhGH increased FFM and nonoxidative leucine disposal (NOLD; an index of protein synthesis) (P < 0.02), whereas FFM and NOLD were correlated in the fed state (r = 0.81, P = 0.015). With rhGH administration, leucine release from protein breakdown (an index of proteolysis) decreased in the fed compared with fasting states (P = 0.012), which was not observed with the placebo. However, the fast-to-fed difference in leucine release from protein breakdown was not significantly different between rhGH and placebo (P = 0.093). With rhGH, the intestinal absorption of leucine and glutamine increased (P = 0.036) and correlated with serum insulin (r = 0.91, P = 0.002). rhGH increased glutamine de novo synthesis (P < 0.02) and plasma concentrations (P < 0.03) in both fasting and fed states. CONCLUSIONS In SBS-IF patients, feeding fails to decrease proteolysis in contrast to what is physiologically observed in healthy subjects. rhGH enhances FFM through the stimulation of protein synthesis and might decrease proteolysis in response to feeding. Improvements in de novo synthesis and intestinal absorption increase glutamine availability over the physiologic range, suggesting that beneficial effects of rhGH in hyperphagic patients might be achieved without glutamine supplementation.
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Glucose absorption in small intestinal diseases.
Thazhath, SS, Wu, T, Young, RL, Horowitz, M, Rayner, CK
Expert review of gastroenterology & hepatology. 2014;(3):301-12
Abstract
Recent developments in the field of diabetes and obesity management have established the central role of the gut in glucose homeostasis; not only is the gut the primary absorptive site, but it also triggers neurohumoral feedback responses that regulate the pre- and post-absorptive phases of glucose metabolism. Structural and/or functional disorders of the intestine have the capacity to enhance (e.g.: diabetes) or inhibit (e.g.: short-gut syndrome, critical illness) glucose absorption, with potentially detrimental outcomes. In this review, we first describe the normal physiology of glucose absorption and outline the methods by which it can be quantified. Then we focus on the structural and functional changes in the small intestine associated with obesity, critical illness, short gut syndrome and other malabsorptive states, and particularly Type 2 diabetes, which can impact upon carbohydrate absorption and overall glucose homeostasis.
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[Impact of bariatric surgery on the absorption of nutrients in patients with obesity].
Bodunova, NA, Sabel'nikova, EA, Parfenov, AI
Terapevticheskii arkhiv. 2013;(10):98-104
Abstract
The review considers disturbed metabolism of vitamins, minerals, and protein in patients following bariatric surgery. The positive effect of the surgery is proven; however, postresection syndromes that may further occur determine not only a patient follow-up, but also timely therapeutic interventions to prevent hypovitaminoses, anemia, and mineral metabolic disturbances. There are conflicting data on the incidence of these abnormalities. No guidelines for their treatment and prevention have been elaborated.
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[An inhibitor of intestinal cholesterol transporter].
Sano, M
Nihon rinsho. Japanese journal of clinical medicine. 2013;(9):1661-6
Abstract
Ezetimibe is a unique inhibitor of intestinal cholesterol absorption. Ezetimibe selectively inhibits intestinal cholesterol absorption by blocking Niemann-Pick C1-like 1 (NPCIL1). Ezetimibe accelerates VLDL and TG degradation. Therefore, ezetimibe ameliorates postprandial hyperlipidemia. Ezetimibe inhibited the progression of nonalcoholic fatty liver disease (NAFLD) by correcting insulin resistance and decreasing small dense LDL-C in human subjects. In clinical study, ezetimibe administration combined with statin failed to inhibit progression of IMT thickness in ENHANCE (Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression) study. In this study baseline IMT thickness (0.7 mm) of patients was within normal range. Therefore only two years observation was too short to demonstrate anti-atherogenic effects of ezetimibe. SEAS(Simvastatin and Ezetimibe in Aortic Stenosis) trial examined effects of combination therapy with ezetimibe and statin in patients with aortic stenosis. Combination therapy could not inhibit progression of aortic stenosis. However, events of ischemic heart disease, especially CABG were significantly decreased only in combination group. Statin was not reported to reduce CVD(cardiovascular disease) in moderate to severe CKD patients. In SHARP(Study of Heart and Renal Protection) study, patients with severe renal disease were allocated either for statin alone group or combination therapy group with statin and ezetimibe. Combination therapy significantly decreased non-hemorrhagic stroke by 25 % compared with statin alone group in severe CKD and HD(hemodialysis) patients. Ezetimibe has unique lipid lowering profile increasing HDL-C concomitant with decreasing LDL-C and TG. Ezetimibe should be initiated first in patients with insulin resistant metabolic syndrome. Ezetimibe should be combined with statin to reduce not only LDL-C but RLP-C(remnant like lipoprotein particle choletserol) in type IIb dyslipidemia.
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[Absorption and digestion in metabolic syndrome].
Urita, Y, Takemoto, I, Nakajima, H, Shimada, N, Sugimoto, M
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology. 2011;(4):553-63
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10.
Possible links between intestinal permeability and food processing: A potential therapeutic niche for glutamine.
Rapin, JR, Wiernsperger, N
Clinics (Sao Paulo, Brazil). 2010;(6):635-43
Abstract
Increased intestinal permeability is a likely cause of various pathologies, such as allergies and metabolic or even cardiovascular disturbances. Intestinal permeability is found in many severe clinical situations and in common disorders such as irritable bowel syndrome. In these conditions, substances that are normally unable to cross the epithelial barrier gain access to the systemic circulation. To illustrate the potential harmfulness of leaky gut, we present an argument based on examples linked to protein or lipid glycation induced by modern food processing. Increased intestinal permeability should be largely improved by dietary addition of compounds, such as glutamine or curcumin, which both have the mechanistic potential to inhibit the inflammation and oxidative stress linked to tight junction opening. This brief review aims to increase physician awareness of this common, albeit largely unrecognized, pathology, which may be easily prevented or improved by means of simple nutritional changes.