Activation of sodium-glucose cotransporter 1 ameliorates hyperglycemia by mediating incretin secretion in mice

2009 ◽  
Vol 297 (6) ◽  
pp. E1358-E1365 ◽  
Author(s):  
Ryuichi Moriya ◽  
Takashi Shirakura ◽  
Junko Ito ◽  
Satoshi Mashiko ◽  
Toru Seo

Glucose ingestion stimulates the secretion of the incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). Despite the critical role of incretins in glucose homeostasis, the mechanism of glucose-induced incretin secretion has not been established. We investigated the underlying mechanism of glucose-induced incretin secretion in vivo in mice. Injection of glucose at 1 g/kg in the upper intestine significantly increased plasma GIP and GLP-1 levels, whereas injection of glucose in the colon did not increase GIP or GLP-1 levels. This finding indicates that the glucose sensor for glucose-induced incretin secretion is in the upper intestine. Coadministration of a sodium-glucose cotransporter-1 (SGLT1) inhibitor, phloridzin, with glucose in the upper intestine blocked glucose absorption and glucose-induced incretin secretion. α-methyl-d-glucopyranoside (MDG), an SGLT1 substrate that is a nonmetabolizable sugar, significantly increased plasma GIP and GLP-1 levels, whereas phloridzin blocked these increases, indicating that concomitant transport of sodium ions and glucose (substrate) via SGLT1 itself triggers incretin secretion without the need for subsequent glucose metabolism. Interestingly, oral administration of MDG significantly increased plasma GIP, GLP-1, and insulin levels and reduced blood glucose levels during an intraperitoneal glucose tolerance test. Furthermore, chronic MDG treatment in drinking water (3%) for 13 days reduced blood glucose levels after a 2-h fast and in an oral glucose tolerance test in diabetic db/db mice. Our findings indicate that SGLT1 serves as the intestinal glucose sensor for glucose-induced incretin secretion and that a noncalorigenic SGLT1 substrate ameliorates hyperglycemia by stimulating incretin secretion.

2015 ◽  
Vol 10 (2) ◽  
pp. 326 ◽  
Author(s):  
Emordi Jonathan Emeka ◽  
Agbaje Esther Oluwatoyin ◽  
Oreagba Ibrahim Adekunle ◽  
Iribhogbe Osede Ignis

<p>The purpose of this study is to evaluate the hypoglycaemic properties and preliminary phytochemical screening of <em>Uveria chamae</em>. The hypoglycaemic properties of <em>Uveria chamae</em> was assessed on normoglycaemic rat that received single dose of the extract at 250 and 500 mg/kg body weight and blood glucose levels estimated at 2, 4, and 6 hours (single dose study). The hypoglycaemic property of the extract was also evaluated in normoglycemic rats by oral glucose tolerance test. Phytochemical screening of the extract for the presence of secondary metabolites was performed with standard methods. The extract showed a significant (p&lt;0.05) reduction in blood glucose levels at 2h and 6h compared to control.  The oral glucose tolerance test  result also showed a significant decrease (p&lt;0.05) in blood glucose levels . The study showed that the extract, <em>Uveria chamae</em> has hypoglycaemic properties which may be accounted for by the presence of the phytochemicals.</p><p> </p>


1983 ◽  
Vol 104 (4_Suppl) ◽  
pp. S11-S17
Author(s):  
Bengt Scherstén ◽  
Per-Olof Bitzén

ABSTRACT. The procedure for diagnosing diabetes mellitus when accompanied by classical symptoms is based on random blood glucose levels of 7 mmol/l or more. Problem of diagnosing diabetes in the asymptomatic subject remains difficult. A procedure based on fasting blood glucose levels below 5.5 mmol/l in normals and reproducible values at or above 7 mmol/l in diabetics is proposed. In cases with fasting blood glucose values between 5.5 and 7 mmol/l standardized oral glucose tolerance test is recommended. The diagnostic criteria for normality, impaired glucose tolerance and for diabetes are evaluated against the results of a 10–14 years prospective study.


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253047
Author(s):  
Rosa Maria Rahmi ◽  
Priscila de Oliveira ◽  
Luciano Selistre ◽  
Paulo Cury Rezende ◽  
Gabriela Neuvald Pezzella ◽  
...  

Objective The objective of the present study was to compare 24-hour glycemic levels between obese pregnant women with normal glucose tolerance and non-obese pregnant women. Methods In the present observational, longitudinal study, continuous glucose monitoring was performed in obese pregnant women with normal oral glucose tolerance test with 75 g of glucose between the 24th and the 28th gestational weeks. The control group (CG) consisted of pregnant women with normal weight who were selected by matching the maternal age and parity with the same characteristics of the obese group (OG). Glucose measurements were obtained during 72 hours. Results Both the groups were balanced in terms of baseline characteristics (age: 33.5 [28.7–36.0] vs. 32.0 [26.0–34.5] years, p = 0.5 and length of pregnancy: 25.0 [24.0–25.0] vs. 25.5 [24.0–28.0] weeks, p = 0.6 in the CG and in the OG, respectively). Pre-breakfast glycemic levels were 77.77 ± 10.55 mg/dL in the CG and 82.02 ± 11.06 mg/dL in the OG (p<0.01). Glycemic levels at 2 hours after breakfast were 87.31 ± 13.10 mg/dL in the CG and 93.48 ± 18.74 mg/dL in the OG (p<0.001). Daytime blood glucose levels were 87.6 ± 15.4 vs. 93.1 ± 18.3 mg/dL (p<0.001) and nighttime blood glucose levels were 79.3 ± 15.8 vs. 84.7 ± 16.3 mg/dL (p<0.001) in the CG and in the OG, respectively. The 24-hour, daytime, and nighttime values of the area under the curve were higher in the OG when compared with the CG (85.1 ± 0.16 vs. 87.9 ± 0.12, 65.6 ± 0.14 vs. 67.5 ± 0.10, 19.5 ± 0.07 vs. 20.4 ± 0.05, respectively; p<0.001). Conclusion The results of the present study showed that obesity in pregnancy was associated with higher glycemic levels even in the presence of normal findings on glucose tolerance test.


2020 ◽  
Vol 10 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Morad Hebi ◽  
Mohamed Eddouks

Background: Corrigiola telephiifolia Pourr, is a perennial species, woody distributed throughout the north of Africa. This plant is used in traditional Mediterranean preparations and has many traditional uses especially treatment of diabetes. Aim/Methods: The current research was carried out to evaluate the antidiabetic effect of Aerial Parts of Aqueous Extract (APAE) of Corrigiola telephiifolia (C. telephiifolia) on both normal and streptozotocin (STZ)-induced diabetic rats treated at a dose of 5 mg/kg for fifteen days. Additionally, the histopathological changes in the liver, morphometric analysis, Oral Glucose Tolerance Test (OGTT) in normal rats and preliminary phytochemical screening for various components were realized. Results: Single oral administration of the APAE of C. telephiifolia (5mg/kg) showed no significant change in glycaemia of normal and STZ-induced diabetic rats. In contrast, repeated oral administration of C. telephiifolia reduced blood glucose levels from 4.11 ± 0.10 mmol/L to 3.16 ± 0.16 mmol/L (p<0.01) 15 days after administration in normal rats. Furthermore, blood glucose levels decreased from 17.84 ± 1.75mmol/L to 1.93 ± 0.33 mmol/L (p<0.0001) in STZ diabetic rats after fifteen days of treatment. According to the oral glucose tolerance test, C. telephiifolia (5 mg/kg) was shown to prevent significantly the increase in blood glucose levels in normal treated rats 30 min after glucose administration when compared to the control group. Also, the liver architecture of diabetic rats treated by C. telephiifolia was improved when compared with the liver architecture of untreated diabetic rats. Concerning the preliminary phytochemical screening of C. telephiifolia, several compounds have been found such as polyphenols, flavonoids, saponins, mucilage and terpenoids. Conclusion: The results show that the aqueous extract of C. telephiifolia possesses significant antihyperglycemic activity.


1995 ◽  
Vol 28 (4) ◽  
pp. 405-407 ◽  
Author(s):  
Jackson Mauricio Lopes Costa ◽  
Marta Solange C. Moraes ◽  
Ana Cristina R. Saldanha ◽  
Aldina Barral ◽  
Marcelo N. Burattini

The authors report a case of a male patient from Bacabal, MA with diffuse cutaneous leishmaniasis (DCL), for at least nine years, with 168 lesions on his body. These were tumour-like nodules with some ulceratmi. He usedpentavalent antimonial (glucantime®) and an association of gamma interferon plus glucantime with improvement of the lesions but relapsed later. Recently, pentamidine isethionate (pentacarinat®) was given a dosage of 4mg/kg/weight/day on alternate days for 20 applications. After 3 months a similar course of 10 application was given 2 times. Later he developed diabetic signs with weight loss of 10kg, polydypsia, polyuria and xerostomia. The lower limbs lesions showed signs of activity. Blood glucose levels normalised and remain like this at moment. Attention is drawn to the fact that pentamidine isethionate should be used as a therapy option with care, obeyng rigorous laboratory controls including a glucose tolerance test.


2008 ◽  
Vol 93 (12) ◽  
pp. 4909-4916 ◽  
Author(s):  
Marzieh Salehi ◽  
Torsten P. Vahl ◽  
David A. D'Alessio

Background: Exogenous administration of glucagon-like peptide (GLP)-1 improves glucose tolerance by stimulation of insulin secretion, inhibition of glucagon secretion, and delay of gastric emptying. It is not known which of these effects is involved in the action of endogenous GLP-1 to control blood glucose. To determine the role of endogenous GLP-1 on islet cell function and gastric emptying independent of variable glycemia, we clamped blood glucose before and during glucose ingestion with and without GLP-1 receptor blockade with exendin-[9–39] (Ex-9). Methods: There were 10 healthy subjects that participated in two experiments each, one a control and one with infusion of 750 pm/kg · min Ex-9. Subjects consumed 75 g oral glucose solution mixed with d-xylose and 13C-glucose while their blood glucose levels were held fixed at approximately 8.9 mmol/liter. Results: Plasma insulin levels during hyperglycemia alone were similar in the two studies (control, 282.5 ± 42 vs. Ex-9, 263.8 ± 59 pmol/liter) but were reduced by approximately 30% by Ex-9 after glucose ingestion (control, 1154 ± 203 vs. Ex-9, 835 ± 120 pmol/liter; P &lt; 0.05). Blocking the action of endogenous GLP-1 caused an approximate 80% increase in postprandial glucagon concentrations. The appearance of ingested d-xylose in the blood was not affected by Ex-9, suggesting that postprandial secretion of GLP-1 has only minimal effects on gastric emptying of oral glucose. Conclusions: These findings indicate that GLP-1 is an incretin in healthy humans at modestly supraphysiological blood glucose levels. The primary effect of GLP-1 to regulate oral glucose tolerance is mediated by effects on islet hormones and not on gastric emptying.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Zhi-Long Shi ◽  
Yi-Dan Liu ◽  
Yun-Yun Yuan ◽  
Da Song ◽  
Mei-Feng Qi ◽  
...  

Norathyriol is a metabolite of mangiferin. Mangiferin has been reported to inhibit α-glucosidase. To the best of our knowledge, no study has been conducted to determine or compare those two compounds on inhibiting α-glucosidase in vitro and in vivo by far. In this study, we determined the inhibitory activity of norathyriol and mangiferin on α-glucosidase in vitro and evaluated their antidiabetic effect in diabetic mice. The results showed that norathyriol inhibited α-glucosidase in a noncompetitive manner with an IC50 value of 3.12 μM, which is more potent than mangiferin (IC50 = 358.54 μM) and positive drug acarbose (IC50 = 479.2 μM) in the zymological experiment. Both of norathyriol and mangiferin caused significant (p<0.05) reduction in fasting blood glucose and the blood glucose levels at two hours after carbohydrate loading and it was interesting that mangiferin and norathyriol can make the decline of the blood glucose earlier than other groups ever including normal group in the starch tolerance test. However, norathyriol and mangiferin did not significantly influence carbohydrate absorption in the glucose tolerance test. Therefore, the antidiabetic effects of norathyriol and mangiferin might be associated with α-glucosidase, and norathyriol was more potent than mangiferin.


Sign in / Sign up

Export Citation Format

Share Document