KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state

Glucose-dependent insulinotropic polypeptide (GIP), a gut hormone secreted from intestinal K-cells, potentiates insulin secretion. Both K-cells and pancreatic β-cells are glucose-responsive and equipped with a similar glucose-sensing apparatus that includes glucokinase and an ATP-sensitive K+(KATP) channel comprising KIR6.2 and sulfonylurea receptor 1. In absorptive epithelial cells and enteroendocrine cells, sodium glucose co-transporter 1 (SGLT1) is also known to play an important role in glucose absorption and glucose-induced incretin secretion. However, the glucose-sensing mechanism in K-cells is not fully understood. In this study, we examined the involvement of SGLT1 (SLC5A1) and the KATPchannels in glucose sensing in GIP secretion in both normal and streptozotocin-induced diabetic mice. Glimepiride, a sulfonylurea, did not induce GIP secretion and pretreatment with diazoxide, a KATPchannel activator, did not affect glucose-induced GIP secretion in the normal state. In mice lacking KATPchannels (Kir6.2−/−mice), glucose-induced GIP secretion was enhanced compared with control (Kir6.2+/+) mice, but was completely blocked by the SGLT1 inhibitor phlorizin. InKir6.2−/−mice, intestinal glucose absorption through SGLT1 was enhanced compared with that inKir6.2+/+mice. On the other hand, glucose-induced GIP secretion was enhanced in the diabetic state inKir6.2+/+mice. This GIP secretion was partially blocked by phlorizin, but was completely blocked by pretreatment with diazoxide in addition to phlorizin administration. These results demonstrate that glucose-induced GIP secretion depends primarily on SGLT1 in the normal state, whereas the KATPchannel as well as SGLT1 is involved in GIP secretion in the diabetic statein vivo.

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Inhibition of α-Glucosidase, Intestinal Glucose Absorption, and Antidiabetic Properties by Caralluma europaea

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/9589472 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Hayat Ouassou ◽

Touda Zahidi ◽

Saliha Bouknana ◽

Mohamed Bouhrim ◽

Hassane Mekhfi ◽

...

Keyword(s):

Ethyl Acetate Fraction ◽

Inhibitory Effect ◽

Tolerance Test ◽

Glucose Absorption ◽

Significant Inhibition ◽

Oral Glucose ◽

Glucosidase Activity ◽

Intestinal Glucose Absorption

Many medicinal plants around the world are used for therapeutic purposes against several diseases, including diabetes mellitus. Due to their composition of natural substances that are effective and do not represent side effects for users, unlike synthetic drugs, in this study, we investigated the inhibitory effect of Caralluma europaea (CE) on α-glucosidase activity in vitro; then the kinetics of the enzyme were studied with increasing concentrations of sucrose in order to determine the inhibition type of the enzyme. In addition, this effect of Caralluma europaea (CE) was confirmed in vivo using rats as an experimental animal model. Among the five fractions of CE, only the ethyl acetate fraction of C. europaea (EACe) induced a significant inhibition of α-glucosidase and its inhibition mode was competitive. The in vivo studies were conducted on mice and rats using glucose and sucrose as a substrate, respectively, to determine the oral glucose tolerance test (OGTT). The results obtained showed that the EACe and the aqueous extract of C. europaea (AECe) have significantly reduced the postprandial hyperglycemia after sucrose and glucose loading in normal and diabetic rats. AECe, also, significantly decreased intestinal glucose absorption, in situ. The results obtained showed that Caralluma europaea has a significant antihyperglycemic activity, which could be due to the inhibition of α-glucosidase activity and enteric absorption of glucose.

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Intestinal glucose sensing and regulation of intestinal glucose absorption

Biochemical Society Transactions ◽

10.1042/bst0351191 ◽

2007 ◽

Vol 35 (5) ◽

pp. 1191-1194 ◽

Cited By ~ 61

Author(s):

J. Dyer ◽

K. Daly ◽

K.S.H. Salmon ◽

D.K. Arora ◽

Z. Kokrashvili ◽

...

Keyword(s):

Sugar Content ◽

Short Review ◽

Glucose Absorption ◽

Glucose Sensing ◽

Sugar Sensing ◽

Sensing System ◽

Glucose Homoeostasis ◽

Luminal Membrane ◽

Intestinal Glucose Absorption ◽

Dietary Sugars

SGLT1 (Na+/glucose co-transporter 1) transports the dietary sugars, D-glucose and D-galactose, from the lumen of the intestine into enterocytes. SGLT1 regulation has important consequences for the provision of glucose to the respiring tissues and is therefore essential for maintaining glucose homoeostasis. SGLT1 expression is directly regulated in response to changes in the sugar content of the diet. To monitor these variations, there is a requirement for a glucose-sensing system located on the luminal membrane of gut cells. This short review focuses on recent findings on intestinal sugar sensing and the downstream mechanisms responsible for enhancement in SGLT1 expression.

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Response to Comment on: Gorboulev et al. Na+-D-glucose Cotransporter SGLT1 Is Pivotal for Intestinal Glucose Absorption and Glucose-Dependent Incretin Secretion. Diabetes 2012;61:187-196

Diabetes ◽

10.2337/db12-0061 ◽

2012 ◽

Vol 61 (6) ◽

pp. e5-e5 ◽

Cited By ~ 3

Author(s):

H. Koepsell ◽

V. Gorboulev

Keyword(s):

Glucose Absorption ◽

Incretin Secretion ◽

Intestinal Glucose Absorption

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PL3. Duodenal Glucose Sensing and Regulation of Intestinal Glucose Absorption After Roux-en-Y Gastric Bypass

Journal of Surgical Research ◽

10.1016/j.jss.2008.11.134 ◽

2009 ◽

Vol 151 (2) ◽

pp. 226-227 ◽

Cited By ~ 1

Author(s):

A.T. Stearns ◽

A. Balakrishnan ◽

D.B. Rhoads ◽

S.W. Ashley ◽

A. Tavakkolizadeh

Keyword(s):

Gastric Bypass ◽

Glucose Absorption ◽

Glucose Sensing ◽

Intestinal Glucose Absorption

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Annona muricata L. extract decreases intestinal glucose absorption and improves glucose tolerance in normal and diabetic rats

Journal of Herbmed Pharmacology ◽

10.34172/jhp.2021.42 ◽

2021 ◽

Vol 10 (3) ◽

pp. 359-366

Author(s):

Ana María Guevara-Vásquez ◽

Julio Víctor Campos-Florián ◽

Jesús Haydee Dávila-Castillo

Keyword(s):

Aqueous Extract ◽

Leaf Extract ◽

Glucose Absorption ◽

Diabetic Rats ◽

Annona Muricata ◽

Antihyperglycemic Activity ◽

Aqueous Leaf Extract ◽

Intestinal Glucose Absorption

Introduction: Poorly controlled hyperglycemia causes numerous health complications. Postprandial hyperglycemia is an important indicator of diabetic status. The aim of this research was to evaluate the effect of Annona muricata L. extract on the in vitro intestinal glucose absorption in diabetic rats and in vivo antihyperglycemic activity in both normal and diabetic rats. Methods: Phytochemical screening of the aqueous extract from the leaves of A. muricata was carried out. Albino rats were randomly assigned into normal and diabetic groups. Each group was divided into three subgroups: control (vehicle), experimental (A. muricata), and standard (Metformin) groups, to determine antihyperglycemic activity at different times after glucose overload. The everted intestinal sac technique was used to study intestinal glucose absorption in diabetic rats. Results: Aqueous leaf extract of Peruvian A. muricata exhibited statistically significant (P < 0.05) in vivo antihyperglycemic activity in both normal and diabetic rats when compared to the control group. The magnitude of the effect was similar to metformin treatment. Moreover, the aqueous leaf extract of A. muricata significantly diminished in vitro intestinal glucose absorption, with a magnitude similar to metformin treatment. Phytochemical analysis of the aqueous extract revealed the presence of tannins, flavonoids, alkaloids, and leucoanthocyanidins, among others. Conclusion: This study reveals that A. muricata aqueous extract is able to reduce in vitro intestinal glucose absorption and improve oral glucose tolerance in rats.

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Chemical Composition Analysis Using HPLC-UV/GC-MS and Inhibitory Activity of Different Nigella sativa Fractions on Pancreatic α-Amylase and Intestinal Glucose Absorption

BioMed Research International ◽

10.1155/2021/9979419 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Mohammed Dalli ◽

Nour Elhouda Daoudi ◽

Salah-eddine Azizi ◽

Hind Benouda ◽

Mohamed Bnouham ◽

...

Keyword(s):

Chemical Composition ◽

Nigella Sativa ◽

Inhibitory Effect ◽

Glucose Absorption ◽

Hexane Fraction ◽

Composition Analysis ◽

Aqueous Fraction ◽

Intestinal Glucose Absorption

Nigella sativa (NS) is a well-known plant for its various benefits and multiuse in traditional medicine. This study is aimed at investigating the chemical composition of the different NS fractions by using GC-MS for the esterified fatty acids or HPLC-UV for organic fraction and at evaluating the inhibitory effect on pancreatic α-amylase (in vitro, in vivo) and intestinal glucose absorption. Among all the investigated fractions, it was shown that they are rich with different molecules of great interest. The n-hexane fraction was characterized by the presence of linoleic acid (44.65%), palmitic acid (16.32%), stearic acid (14.60%), and thymoquinone (8.7%), while among the identified peaks in EtOH fraction we found catechin (89.03 mg/100 g DW), rutin (6.46 mg/100 g DW), and kaempferol (0.032 mg/100 g DW). The MeOH fraction was distinguished with the presence of gallic acid (19.91 mg/100 g DW), catechin (13.79 mg/100 g DW), and rutin (21.07 mg/100 g DW). Finally, the aqueous fraction was marked by the existence of different molecules; among them, we mention salicylic acid (32.26 mg/100 g DW), rutin (21.46 mg/100 g DW), and vanillic acid (3.81 mg/100 g DW). Concerning the inhibitory effect on pancreatic α-amylase, it was found that in the in vitro study, the best IC50 registered were those of EtOH (0.25 mg/ml), MeOH (0.10 mg/ml), aqueous (0.031 mg/ml), and n-hexane fraction (0.76 mg/ml), while in the in vivo study an important inhibition of α-amylase in normal and diabetic rats was observed. Finally, the percentage of intestinal glucose absorption was evaluated for all tested extracts and it was ranging from 24.82 to 60.12%. The results of the present study showed that the NS seed fractions exert an interesting inhibitory effect of α-amylase and intestinal glucose absorption activity which could be associated with the existent bioactive compounds. Indeed, these compounds can be used as antidiabetic agents because of their nontoxic effect and high efficacy.

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Comment on: Gorboulev et al. Na+-D-glucose Cotransporter SGLT1 Is Pivotal for Intestinal Glucose Absorption and Glucose-Dependent Incretin Secretion. Diabetes 2012;61:187-196

Diabetes ◽

10.2337/db11-1793 ◽

2012 ◽

Vol 61 (6) ◽

pp. e4-e4 ◽

Cited By ~ 5

Author(s):

G. L. Kellett

Keyword(s):

Glucose Absorption ◽

Incretin Secretion ◽

Intestinal Glucose Absorption

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Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes

Acta Endocrinologica ◽

10.1530/eje-06-0756 ◽

2007 ◽

Vol 156 (6) ◽

pp. 663-671 ◽

Cited By ~ 43

Author(s):

Lotte B Nielsen ◽

Kenneth B Ploug ◽

Peter Swift ◽

Cathrine Ørskov ◽

Inger Jansen-Olesen ◽

...

Keyword(s):

Type 1 Diabetes ◽

Glycaemic Control ◽

Glucose Sensing ◽

Onset Type ◽

K Cells ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

New Onset

Objective: The ATP-dependent K+-channel (KATP) is critical for glucose sensing and normal glucagon and insulin secretion from pancreatic endocrine α- and β-cells. Gastrointestinal endocrine L- and K-cells are also glucose-sensing cells secreting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) respectively. The aims of this study were to 1) investigate the expression and co-localisation of the KATP channel subunits, Kir6.2 and SUR1, in human L- and K-cells and 2) investigate if a common hyperactive variant of the Kir6.2 subunit, Glu23Lys, exerts a functional impact on glucose-sensing tissues in vivo that may affect the overall glycaemic control in children with new-onset type 1 diabetes. Design and methods: Western blot and immunohistochemical analyses were performed for expression and co-localisation studies. Meal-stimulated C-peptide test was carried out in 257 children at 1, 6 and 12 months after diagnosis. Genotyping for the Glu23Lys variant was by PCR-restriction fragment length polymorphism. Results: Kir6.2 and SUR1 co-localise with GLP-1 in L-cells and with GIP in K-cells in human ileum tissue. Children with type 1 diabetes carrying the hyperactive Glu23Lys variant had higher HbA1C at bdiagnosis (coefficient = 0.61%, P = 0.02) and 1 month after initial insulin therapy (coefficient = 0.30%, P = 0.05), but later disappeared. However, when adjusting HbA1C for the given dose of exogenous insulin, the dose-adjusted HbA1C remained higher throughout the 12 month study period (coefficient = 0.42%, P = 0.03). Conclusions: Kir6.2 and SUR1 co-localise in the gastrointestinal endocrine L- and K-cells. The hyperactive Glu23Lys variant of the KATP channel subunit Kir6.2 may cause defective glucose sensing in several tissues and impaired glycaemic control in children with type 1 diabetes.

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The diffusive component of intestinal glucose absorption is mediated by the glucose-induced recruitment of GLUT2 to the brush-border membrane

Biochemical Journal ◽

10.1042/bj3500155 ◽

2000 ◽

Vol 350 (1) ◽

pp. 155-162 ◽

Cited By ~ 153

Author(s):

George L. KELLETT ◽

Philip A. HELLIWELL

Keyword(s):

Brush Border ◽

Glucose Concentration ◽

Brush Border Membrane ◽

Glucose Absorption ◽

Facilitated Diffusion ◽

Simple Diffusion ◽

Saturation Kinetics ◽

Intestinal Glucose Absorption ◽

Diffusive Component

We have investigated the mechanism responsible for the diffusive component of intestinal glucose absorption, the major route by which glucose is absorbed. In perfused rat jejunum in vivo, absorption was strongly inhibited by phloretin, an inhibitor of GLUT2. The GLUT2 level at the brush-border membrane increased some 2-fold when the luminal glucose concentration was changed from 0 to 100mM. The phloretin-sensitive or diffusive component of absorption appeared superficially linear and consistent with simple diffusion, but was in fact carrier-mediated and co-operative (n = 1.6, [G1/2] = 56mM; where [G1/2] is the glucose concentration at half Vmax) because of the glucose-induced activation and recruitment of GLUT2 to the brush-border membrane. Diffusive transport by paracellular flow was negligible. The phloretin-insensitive, SGLT1-mediated, component of glucose absorption showed simple saturation kinetics with [G1/2] = 27mM: the activation of protein kinase C (PKC) βII, the isoenzyme of PKC that most probably controls GLUT2 trafficking [Helliwell, Richardson, Affleck and Kellett (2000) Biochem. J. 350, 149–154], also showed simple saturation kinetics, with [G1/2] = 21mM. We conclude that the principal route for glucose absorption is by GLUT2-mediated facilitated diffusion across the brush-border membrane, which is up to 3-fold greater than that by SGLT1; the magnitude of the diffusive component at any given glucose concentration correlates with the SGLT1-dependent activation of PKC βII. The implications of these findings for the assimilation of sugars immediately after a meal are discussed.

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