Sitagliptin prevents the development of metabolic and hormonal disturbances, increased β-cell apoptosis and liver steatosis induced by a fructose-rich diet in normal rats

The aim of the present study was to test the effect of sitagliptin and exendin-4 upon metabolic alterations, β-cell mass decrease and hepatic steatosis induced by F (fructose) in rats. Normal adult male Wistar rats received a standard commercial diet without (C) or with 10% (w/v) F in the drinking water (F) for 3 weeks; animals from each group were randomly divided into three subgroups: untreated (C and F) and simultaneously receiving either sitagliptin (CS and FS; 115.2 mg/day per rat) or exendin-4 (CE and FE; 0.35 nmol/kg of body weight, intraperitoneally). Water and food intake, oral glucose tolerance, plasma glucose, triacylglycerol (triglyceride), insulin and fructosamine concentration, HOMA-IR [HOMA (homoeostasis model assessment) for insulin resistance], HOMA-β (HOMA for β-cell function) and liver triacylglycerol content were measured. Pancreas immunomorphometric analyses were also performed. IGT (impaired glucose tolerance), plasma triacylglycerol, fructosamine and insulin levels, HOMA-IR and HOMA-β indexes, and liver triacylglycerol content were significantly higher in F rats. Islet β-cell mass was significantly lower in these rats, due to an increase in the percentage of apoptosis. The administration of exendin-4 and sitagliptin to F animals prevented the development of all the metabolic disturbances and the changes in β-cell mass and fatty liver. Thus these compounds, useful in treating Type 2 diabetes, would also prevent/delay the progression of early metabolic and tissue markers of this disease.

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Glucose metabolic disorder in Klinefelter syndrome: a retrospective analysis in a single Chinese hospital and literature review

BMC Endocrine Disorders ◽

10.1186/s12902-021-00893-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shixuan Liu ◽

Tao Yuan ◽

Shuoning Song ◽

Shi Chen ◽

Linjie Wang ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Literature Review ◽

Glucose Tolerance ◽

Cell Function ◽

Klinefelter Syndrome ◽

Oral Glucose ◽

Model Assessment ◽

Β Cell ◽

Β Cell Function

Abstract Background We aimed to investigate the clinical characteristics and islet β-cell function in patients with Klinefelter syndrome (KS) and hyperglycemia. Methods This is a retrospective study. In total, 22 patients diagnosed with KS were identified from the electronic medical record system, including 9 patients with hyperglycemia (total patients with hyperglycemia, THG-KS group) and 5 hyperglycemic KS patients with oral glucose tolerance test (OGTT) results (HG-KS group). An additional 5 subjects with hyperglycemia and 5 normal glucose tolerance (NGT) subjects matched based on body mass index were included as the HG group and NGT group, respectively. Data from clinical and laboratory examinations were collected. We further performed a literature review of KS and hyperglycemia. Results We found that KS patients developed abnormal glucose metabolism earlier in life than those without KS, and the median age was 17 years, ranging from 10 years to 19 years. Six of 17 (35.3%) patients were diagnosed with diabetes mellitus and 3 of 17 (17.6%) patients were diagnosed with prediabetes. Among 10 patients with both fasting blood glucose and insulin results recorded, there were 8 out of 17 (47.1%) KS patients had insulin resistance. The prevalence of hypertension and dyslipidemia was higher in patients with hyperglycemia and KS than in patients with NGT KS. Compared with the HG group, insulin sensitivity levels were lower in HG-KS group, whereas homeostasis model assessment of β-cell function levels (p = 0.047) were significantly, indicating higher insulin secretion levels in the HG-KS group. Conclusions KS patients develop hyperglycemia earlier in life than those without KS and show lower insulin sensitivity and higher insulin secretion. These patients also have a higher prevalence of other metabolic diseases and may have different frequencies of developing KS-related symptoms.

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Effects of the long-acting somatostatin analogue Lanreotide Autogel on glucose tolerance and insulin resistance in acromegaly

Acta Endocrinologica ◽

10.1530/eje.1.02185 ◽

2006 ◽

Vol 155 (1) ◽

pp. 73-78 ◽

Cited By ~ 40

Author(s):

B Steffin ◽

B Gutt ◽

M Bidlingmaier ◽

C Dieterle ◽

F Oltmann ◽

...

Keyword(s):

Insulin Resistance ◽

Blood Glucose ◽

Glucose Tolerance ◽

Cell Function ◽

Oral Glucose ◽

Model Assessment ◽

Β Cell ◽

Igf I ◽

Β Cell Function ◽

Lanreotide Autogel

Object: Treatment with somatostatin analogues (SA) not only inhibits GH secretion but may also impair insulin secretion. In order to evaluate the influence of SA on glucose metabolism, we investigated insulin resistance (IR) and β-cell function, using the recommended combination of homeostatic model assessment of IR (HOMA-IR) and β-cell function (HOMA-β). Design and methods: This is a prospective, cross-sectional study. We measured fasting insulin, blood glucose and IGF-I. Insulin and blood glucose measurements were taken 120 min after an oral glucose tolerance test with 75 g glucose. We studied 51 patients (27 female/24 male, age 54 years (20–75)). Eighteen patients were on Lanreotide Autogel (LA) treatment, 33 had no medical treatment. GH-levels of more than 2.5 ng/ml was reached by 59% of the patients, 74.5% had normal IGF-I levels. Results: We found no significant influence of disease activity on HOMA-IR and HOMA-β. In the 33 of 51 subjects without any drug treatment, median HOMA-β was 170.4% (36.0–624.0%). In contrast, in the 18 patients on LA treatment, median HOMA-β was found to be significantly lower (84.2% (36.5–346.2%); P = 0.001). Despite this, there was no difference in HOMA-IR in both groups (2.4 (0.7–8.4) vs 2.3 (0.7–6.1); P < 0.001) despite similar insulin values. Conclusion: In conclusion, we found that LA decreases β-cell function significantly without affecting IR. Therefore, we think that insulin secretagogues are probably more effective in the treatment of diabetes mellitus in acromegalic patients on LA therapy than insulin sensitizers.

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The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test: Forerunner of Heightened Glycemic Failure Rates and Accelerated Decline in β-Cell Function in TODAY

Diabetes Care ◽

10.2337/dc18-1122 ◽

2018 ◽

Vol 42 (1) ◽

pp. 164-172 ◽

Cited By ~ 8

Author(s):

Silva Arslanian ◽

Laure El ghormli ◽

Joon Young Kim ◽

Fida Bacha ◽

Christine Chan ◽

...

Keyword(s):

Glucose Tolerance ◽

Response Curve ◽

Glucose Tolerance Test ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Β Cell ◽

Glucose Response ◽

Β Cell Function

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Age-dependent decline in β-cell function assessed by an oral glucose tolerance test-based disposition index

Journal of Diabetes Investigation ◽

10.1111/j.2040-1124.2010.00099.x ◽

2011 ◽

Vol 2 (4) ◽

pp. 293-296 ◽

Cited By ~ 10

Author(s):

Hisako Komada ◽

Kazuhiko Sakaguchi ◽

Kazuo Takeda ◽

Yushi Hirota ◽

Naoko Hashimoto ◽

...

Keyword(s):

Glucose Tolerance ◽

Oral Glucose Tolerance Test ◽

Glucose Tolerance Test ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Β Cell ◽

Age Dependent ◽

Β Cell Function

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Effects of Sucralose Ingestion versus Sucralose Taste on Metabolic Responses to an Oral Glucose Tolerance Test in Participants with Normal Weight and Obesity: A Randomized Crossover Trial

Nutrients ◽

10.3390/nu12010029 ◽

2019 ◽

Vol 12 (1) ◽

pp. 29 ◽

Cited By ~ 4

Author(s):

Alexander D. Nichol ◽

Clara Salame ◽

Kristina I. Rother ◽

M. Yanina Pepino

Keyword(s):

Glucose Tolerance ◽

Cell Function ◽

Normal Weight ◽

Taste Perception ◽

Metabolic Responses ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Β Cell ◽

Β Cell Function ◽

Weight Groups

Here, we tested the hypothesis that sucralose differentially affects metabolic responses to labeled oral glucose tolerance tests (OGTTs) in participants with normal weight and obesity. Participants (10 with normal weight and 11 with obesity) without diabetes underwent three dual-tracer OGTTs preceded, in a randomized order, by consuming sucralose or water, or by tasting and expectorating sucralose (e.g., sham-fed; sweetness control). Indices of β-cell function and insulin sensitivity (SI) were estimated using oral minimal models of glucose, insulin, and C-peptide kinetics. Compared with water, sucralose ingested (but not sham-fed) resulted in a 30 ± 10% increased glucose area under the curve in both weight groups. In contrast, the insulin response to sucralose ingestion differed depending on the presence of obesity: decreased within 20–40 min of the OGTT in normal-weight participants but increased within 90–120 min in participants with obesity. Sham-fed sucralose similarly decreased insulin concentrations within 60 min of the OGTT in both weight groups. Sucralose ingested (but not sham-fed) increased SI in normal-weight participants by 52 ± 20% but did not affect SI in participants with obesity. Sucralose did not affect glucose rates of appearance or β-cell function in either weight group. Our data underscore a physiological role for taste perception in postprandial glucose responses, suggesting sweeteners should be consumed in moderation.

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Impaired β-cell function and decreased insulin sensitivity in subjects with normal oral glucose tolerance but isolated high glycosylated hemoglobin

Endocrine Journal ◽

10.1507/endocrj.ej17-0325 ◽

2018 ◽

Vol 65 (1) ◽

pp. 13-22 ◽

Cited By ~ 1

Author(s):

Qi Fu ◽

Min Sun ◽

Zhixiao Wang ◽

Wei He ◽

Yu Duan ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cell Function ◽

Glycosylated Hemoglobin ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Β Cell ◽

Β Cell Function

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Assessment of β-cell function during the oral glucose tolerance test by a minimal model of insulin secretion

European Journal of Clinical Investigation ◽

10.1046/j.1365-2362.2001.00827.x ◽

2001 ◽

Vol 31 (5) ◽

pp. 405-416 ◽

Cited By ~ 65

Author(s):

A. Cretti ◽

M. Lehtovirta ◽

E. Bonora ◽

B. Brunato ◽

M. G. Zenti ◽

...

Keyword(s):

Insulin Secretion ◽

Glucose Tolerance ◽

Oral Glucose Tolerance Test ◽

Glucose Tolerance Test ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Β Cell ◽

Β Cell Function

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VMP1-related autophagy induced by a fructose-rich diet in β-cells: its prevention by incretins

Clinical Science ◽

10.1042/cs20170010 ◽

2017 ◽

Vol 131 (8) ◽

pp. 673-687 ◽

Cited By ~ 5

Author(s):

Bárbara Maiztegui ◽

Verónica Boggio ◽

Carolina L. Román ◽

Luis E. Flores ◽

Héctor Del Zotto ◽

...

Keyword(s):

Caspase 3 ◽

Cell Function ◽

Cell Damage ◽

Cell Mass ◽

Ultrastructural Changes ◽

Mrna Levels ◽

Model Assessment ◽

Β Cells ◽

Β Cell ◽

Insulin Mrna

The aim of the present study was to demonstrate the role of autophagy and incretins in the fructose-induced alteration of β-cell mass and function. Normal Wistar rats were fed (3 weeks) with a commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, β-cell mass, morphology/ultrastructure and apoptosis, vacuole membrane protein 1 (VMP1) expression and glucose-stimulated insulin secretion (GSIS) were studied. Complementary to this, islets isolated from normal rats were cultured (3 days) without (C) or with F and F + exendin-4 or chloroquine. Expression of autophagy-related proteins [VMP1 and microtubule-associated protein light chain 3 (LC3)], apoptotic/antiapoptotic markers (caspase-3 and Bcl-2), GSIS and insulin mRNA levels were measured. F rats developed impaired glucose tolerance (IGT) and a significant increase in plasma triacylglycerols, thiobarbituric acid-reactive substances, insulin levels, homoeostasis model assessment (HOMA) for insulin resistance (HOMA-IR) and β-cell function (HOMA-β) indices. A significant reduction in β-cell mass was associated with an increased apoptotic rate and morphological/ultrastructural changes indicative of autophagic activity. All these changes were prevented by either sitagliptin or exendin-4. In cultured islets, F significantly enhanced insulin mRNA and GSIS, decreased Bcl-2 mRNA levels and increased caspase-3 expression. Chloroquine reduced these changes, suggesting the participation of autophagy in this process. Indeed, F induced the increase of both VMP1 expression and LC3-II, suggesting that VMP1-related autophagy is activated in injured β-cells. Exendin-4 prevented islet-cell damage and autophagy development. VMP1-related autophagy is a reactive process against F-induced islet dysfunction, being prevented by exendin-4 treatment. This knowledge could help in the use of autophagy as a potential target for preventing progression from IGT to type 2 diabetes mellitus.

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Detection of Glycemic Abnormalities in Young Adult Patients with Beta Thalassemia Major Using Continuous Glucose Monitoring System (CGMS) and Oral Glucose Tolerance Test (OGTT)

Blood ◽

10.1182/blood.v118.21.2158.2158 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2158-2158

Author(s):

Mohamed A. Yassin ◽

Ahmed M Elawa ◽

Ashraf T Soliman

Keyword(s):

Glucose Tolerance ◽

Oral Glucose Tolerance Test ◽

Glucose Tolerance Test ◽

Cell Function ◽

Serum Insulin ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Β Cell ◽

Β Cell Function

Abstract Abstract 2158 Introduction: Both insulin deficiency and insulin resistance are reported in patients with β thalassemia major (BTM). The use of continuous blood glucose monitoring system (CGMS) among the different methods for early detection of glycaemic abnormalities has not been studied thoroughly in these patients. Aims: The aims of this study were: 1. to detect glycaemic abnormalities, if any, in young adults with BTM using fasting blood glucose (FBG), oral glucose tolerance test (OGTT), 72-h continuous glucose concentration by CGMS system, and serum insulin and C-peptide concentrations 2. To compare the results of these two methods in detecting glycaemic abnormalities in these patients and 3. To calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in these patients. In order to evaluate whether glycaemic abnormalities are due to insulin deficiency and/or resistance. Materials and methods: Randomly selected young adults (n = 14) with BTM were the subjects of this study. All patients were investigated using a standard oral glucose tolerance test (OGTT) (using 75 gram of glucose) and 72-h continuous glucose concentration by CGM system (Medtronic system). Fasting serum insulin and C-peptide concentrations were measured and HOMA-B, HOMA-IR were calculated accordingly. Results: Using OGTT, 5 patients had impaired fasting glucose (IFG) (Fasting BG from 5.6 to 6.9 mmol/L). Two of them had impaired glucose tolerance IGT (BG from 7.8 and < 11.1 mmol/L) and one had BG = 16.2 mmol/L after 2-hrs (diabetic). Using CGMS in addition to the glucose data measured by glucometer (3–5 times/ day), 6 patients had IFG. The maximum (postprandial) BG recorded exceeded 11.1 mmol/L in 4 patients (28.5%) (Diabetics) and was > 7.8 but < 11.1 mmol/L in 8 patients (57%) (IGT). The mean values of HOMA and QUICKI in patients with BTM were < 2.6 (1.6± 0.8) and > 0.33 (0.36±0.03) respectively ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B %) on the one hand and the fasting and the 2-h BG (r= −0.6, and − 0.48, P< 0.01 respectively) on the other hand. Serum insulin concentrations were not correlated with fasting BG or ferritin levels. The average and maximum BG levels recorded by CGMS were significantly correlated with the fasting BG (r= 0.69 and 0.6 respectively with P < 0.01) and with the BG at 2-hour after oral glucose intake (r= 0.87and 0.86 respectively with P < 0.01). Ferritin concentrations were positively correlated with the fasting BG and the 2-h BG levels in the OGTT (r= 0.69, 0.43 respectively, P < 0.001) as well as with the average and the maximum BG recorded by CGM (r =0.75, and 0.64 respectively with P < 0.01). Ferritin concentrations were negatively correlated with the β-cell function (r= −0.41, P< 0.01). Conclusion: CGMS has proved to be superior to OGTT for the diagnosis of glycaemic abnormalities in young adult patients with BTM. In our patients, defective β-cell function rather than insulin resistance appeared to be the cause for these abnormalities. The significant correlations between serum ferritin concentrations and the beta cell functions suggested the importance of adequate chelation to prevent β-cell dysfunction Disclosures: No relevant conflicts of interest to declare.

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