Theaflavins prevent the onset of diabetes through ameliorating glucose tolerance mediated by promoted incretin secretion in spontaneous diabetic Torii rats

Background: To investigate the potential synergistic effects of olive oil releasing 2-oleoylglycerol and hydrolyzed pine nut oil containing 20% pinolenic acid on GLP-1 secretion, glucose tolerance, insulin secretion and appetite in healthy individuals, when delivered to the small intestine as potential agonists of GPR119, FFA1 and FFA4. Methods: Nine overweight/obese individuals completed three 6-h oral glucose tolerance tests (OGTTs) in a crossover design. At -30 min, participants consumed either: no oil, 6 g of hydrolyzed pine nut oil (PNO-FFA), or a combination of 3 g hydrolyzed pine nut oil and 3 g olive oil (PNO-OO) in delayed-release capsules. Repeated measures of glucose, insulin, C-peptide, GLP-1, GIP, ghrelin, subjective appetite and gastrointestinal tolerability were done. Results: PNO-FFA augmented GLP-1 secretion from 0–360 min compared to no oil and PNO-OO (p < 0.01). GIP secretion was increased from 240–360 min after both PNO-FFA and PNO-OO versus no oil (p < 0.01). Both oil treatments suppressed subjective appetite by reducing hunger and prospective food consumption and increasing satiety (p < 0.05). Conclusions: In support of previous findings, 6 g of delayed-release hydrolyzed pine nut oil enhanced postprandial GLP-1 secretion and reduced appetite. However, no synergistic effect of combining hydrolyzed pine nut oil and olive oil on GLP-1 secretion was observed. These results need further evaluation in long-term studies including effects on bodyweight and insulin sensitivity.

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Activation of Enteroendocrine Membrane Progesterone Receptors Promotes Incretin Secretion and Improves Glucose Tolerance in Mice

Diabetes ◽

10.2337/db12-0601 ◽

2012 ◽

Vol 62 (1) ◽

pp. 283-290 ◽

Cited By ~ 21

Author(s):

Grace B. Flock ◽

Xiemin Cao ◽

Marlena Maziarz ◽

Daniel J. Drucker

Keyword(s):

Glucose Tolerance ◽

Progesterone Receptors ◽

Incretin Secretion ◽

Membrane Progesterone Receptors

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Identification of a major locus for islet inflammation and fibrosis in the spontaneously diabetic Torii rat

Physiological Genomics ◽

10.1152/physiolgenomics.90214.2008 ◽

2008 ◽

Vol 35 (1) ◽

pp. 96-105 ◽

Cited By ~ 12

Author(s):

Masanori Fuse ◽

Norihide Yokoi ◽

Masami Shinohara ◽

Taku Masuyama ◽

Riko Kitazawa ◽

...

Keyword(s):

Genetic Analysis ◽

Glucose Tolerance ◽

Congenic Strain ◽

Chromosome 3 ◽

Major Locus ◽

Onset Of Diabetes ◽

Trait Locus ◽

Islet Inflammation ◽

Inflammatory Changes ◽

F344 Rats

The pathogenesis of inflammation and fibrosis in the pancreatic islets in diabetes is largely unknown. Spontaneously diabetic Torii (SDT) rats exhibit inflammation and fibrosis in and around the islets during the development of the disease. We investigated genetic factors for diabetes, islet inflammation, and fibrosis in the SDT rat. We produced F1 and F2 rats by intercross between SDT and F344 rats, examined the onset of diabetes, glucose tolerance, and histology of the pancreas, and performed genetic analysis of these traits. We then established a congenic strain carrying the SDT allele at the strongest diabetogenic locus on the F344 genetic background and characterized glucose tolerance and histology of the pancreas. F1 rats showed glucose intolerance and inflammatory changes mainly in the islets. Genetic analysis of diabetes identified a major locus on chromosome 3, designated Dmsdt1, at which a dominantly acting SDT allele was involved. Quantitative trait locus (QTL) analysis of glucose tolerance revealed, in addition to Dmsdt1 [logarithm of odds (LOD) 5.3 near D3Mit12], three other loci, designated Dmsdt2 (LOD 4.2 at D8Rat46), Dmsdt3 (LOD 3.8 near D13Arb5), and Dmsdt4 (LOD 5.8 at D14Arb18). Analysis of a congenic strain for Dmsdt1 indicates that the dominantly acting SDT allele induces islet inflammation and fibrosis. Thus we have found a major locus on chromosome 3 for islet inflammation and fibrosis in the SDT rat. Identification of the genes responsible should provide insight into the pathogenesis of diabetes.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00412.2009 ◽

2009 ◽

Vol 297 (6) ◽

pp. E1358-E1365 ◽

Cited By ~ 101

Author(s):

Ryuichi Moriya ◽

Takashi Shirakura ◽

Junko Ito ◽

Satoshi Mashiko ◽

Toru Seo

Keyword(s):

Blood Glucose ◽

Glucose Tolerance ◽

Glucose Sensor ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Sodium Glucose Cotransporter ◽

Glucose Ingestion ◽

Incretin Secretion

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.

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Ferritin as a Risk Factor for Glucose Intolerance amongst Men and Women Originating from the Indian Subcontinent

International Journal of Endocrinology ◽

10.1155/2015/924387 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Elizabeth A. Hughes ◽

Jeetesh V. Patel ◽

Zosia Bredow ◽

Paramjit S. Gill ◽

Julia Chackathayil ◽

...

Keyword(s):

Blood Pressure ◽

Glucose Tolerance ◽

Glucose Intolerance ◽

Serum Ferritin ◽

Indian Subcontinent ◽

South Asians ◽

Tolerance Test ◽

Oral Glucose ◽

Nonesterified Fatty Acids ◽

Onset Of Diabetes

Background. Serum ferritin predicts the onset of diabetes; however, this relationship is not clear amongst South Asians, a population susceptible to glucose intolerance and anaemia.Objective. This study tests whether ferritin levels reflect glucose tolerance in South Asians, independent of lifestyle exposures associated with Indian or British residence.Methods. We randomly sampled 227 Gujaratis in Britain (49.8 (14.4) years, 50% men) and 277 contemporaries living in Gujarati villages (47.6 (11.8) years, 41% men). Both groups underwent a 75 g oral-glucose-tolerance test. We evaluated lifestyle parameters with standardised questionnaires and conducted comprehensive clinical and lab measurements.Results. Across sites, the age-adjusted prevalence of diabetes was 9.8%. Serum ferritin was higher amongst diabetics (P=0.005), irrespective of site, gender, and central obesity (P≤0.02), and was associated with fasting and postchallenge glucose, anthropometry, blood pressure, triglycerides, and nonesterified fatty acids (P<0.001). Diabetes was less in those with low ferritin (<20 mg/mL),P<0.008, and risk estimate = 0.35 (95% CI 0.15–0.81), as were blood pressure and metabolic risk factors. On multivariate analysis, diabetes was independently associated with ferritin (P=0.001) and age (P<0.001).Conclusion. Ferritin levels are positively associated with glucose intolerance in our test groups, independent of gender and Indian or UK lifestyle factors.

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The impact of low and no-caloric sweeteners on glucose absorption, incretin secretion, and glucose tolerance

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2016-0705 ◽

2017 ◽

Vol 42 (8) ◽

pp. 793-801 ◽

Cited By ~ 11

Author(s):

Catherine B. Chan ◽

Zohre Hashemi ◽

Fatheema B. Subhan

Keyword(s):

Glucose Tolerance ◽

Chronic Administration ◽

Sweet Taste ◽

Glucose Absorption ◽

Metabolic Effects ◽

Binding Properties ◽

Binding Characteristics ◽

Similar Region ◽

Incretin Secretion ◽

The Impact

The consumption of non-nutritive, low, or no-calorie sweeteners (LCS) is increasing globally. Previously thought to be physiologically inert, there is a growing body of evidence that LCS not only provide a sweet taste but may also elicit metabolic effects in the gastrointestinal tract. This review provides a brief overview of the chemical and receptor-binding properties and effects on chemosensation of different LCS but focuses on the extent to which LCS stimulates glucose transport, incretin and insulin secretion, and effects on glucose tolerance. Aspartame and sucralose both bind to a similar region of the sweet receptor. For sucralose, the data are contradictory regarding effects on glucose tolerance in humans and may depend on the food or beverage matrix and the duration of administration, as suggested by longer term rodent studies. For aspartame, there are fewer data. On the other hand, acesulfame-potassium (Ace-K) and saccharin have similar binding characteristics to each other but, while Ace-K may increase incretin secretion and glucose responses in humans, there are no data on saccharin except in rats, which show impaired glucose tolerance after chronic administration. Additional research, particularly of the effects of chronic consumption, is needed to provide concrete evidence for beneficial or detrimental effects of LCS on blood glucose regulation in humans.

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A case of a woman with late-pregnancy-onset DKA who had normal glucose tolerance in the first trimester

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-13-0085 ◽

2014 ◽

Vol 2014 ◽

Cited By ~ 4

Author(s):

Hiromi Himuro ◽

Takashi Sugiyama ◽

Hidekazu Nishigori ◽

Masatoshi Saito ◽

Satoru Nagase ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Glucose Tolerance ◽

Late Pregnancy ◽

First Trimester ◽

Normal Glucose Tolerance ◽

Anion Gap ◽

Normal Glucose ◽

Onset Of Diabetes

Summary Diabetic ketoacidosis (DKA) during pregnancy is a serious complication in both mother and fetus. Most incidences occur during late pregnancy in women with type 1 diabetes mellitus. We report the rare case of a woman with type 1 diabetes mellitus who had normal glucose tolerance during the first trimester but developed DKA during late pregnancy. Although she had initially tested positive for screening of gestational diabetes mellitus during the first trimester, subsequent diagnostic 75-g oral glucose tolerance tests showed normal glucose tolerance. She developed DKA with severe general fatigue in late pregnancy. The patient's general condition improved after treatment for ketoacidosis, and she vaginally delivered a healthy infant at term. The presence of DKA caused by the onset of diabetes should be considered, even if the patient shows normal glucose tolerance during the first trimester. Learning points The presence of DKA caused by the onset of diabetes should be considered, even if the patient shows normal glucose tolerance during the first trimester. Symptoms including severe general fatigue, nausea, and weight loss are important signs to suspect DKA. Findings such as Kussmaul breathing with ketotic odor are also typical. Urinary test, atrial gas analysis, and anion gap are important. If pH shows normal value, calculation of anion gap is important. If the value of anion gap is more than 12, a practitioner should consider the presence of metabolic acidosis.

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Glucose Intolerance and Hyperlipidemia Prior to Diabetes Onset in Female Spontaneously Diabetic Torii (SDT) Rats

Experimental Diabesity Research ◽

10.1080/15438600490898609 ◽

2004 ◽

Vol 5 (4) ◽

pp. 253-256 ◽

Cited By ~ 7

Author(s):

Masami Shinohara ◽

Toshihiro Oikawa ◽

Kahei Sato ◽

Yasunori Kanazawa

Keyword(s):

Glucose Tolerance ◽

Inflammatory Cell ◽

Immunoreactive Insulin ◽

Oral Glucose ◽

Nonesterified Fatty Acids ◽

Oral Glucose Tolerance Tests ◽

Glucose Tolerance Tests ◽

Plasma Immunoreactive Insulin ◽

Onset Of Diabetes

The Spontaneously Diabetic Torii (SDT) rat, a newly established animal model for diabetes mellitus, presents nonobese type 2 diabetes with ocular complications. In the present study, oral glucose tolerance tests and biochemical and histopathological examinations were performed in female SDT rats at 16 and/or 25 weeks of age, before the onset of diabetes. At 25 weeks of age, glucose tolerance was significantly impaired, and plasma immunoreactive insulin levels at 120 min after glucose loading were significantly higher (P< 0.05). Body weight and fasting levels of plasma triglycerides and nonesterified fatty acids were significantly higher than those in control animals. Histopathologically, inflammatory cell infiltration and fibrosis were observed in and around the pancreatic islets. These results strongly suggest that female SDT rats are useful as a model to investigate impairment of glucose tolerance and hyperlipidemia prior to the onset of diabetes.

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