Incretin secretion and glucose metabolism in morbidly obese patients in the early and late periods after biliopancreatic diversion

2016 ◽  
Vol 88 (10) ◽  
pp. 9-18
Author(s):  
I I Dedov ◽  
G A Melnichenko ◽  
E A Troshina ◽  
E V Ershova ◽  
N V Mazurina ◽  
...  

Aim. To estimate the parameters of glucose metabolism and to assess the secretion of incretins in patients after biliopancreatic diversion (BPD) for morbid obesity (MO) in the early and late postoperative periods. Subjects and methods. The prospective part of the investigation included 22 patients with a body mass index of 35.8 to 68.4 kg/m2 and type 2 diabetes mellitus (T2DM). All the patients were examined before, 3 weeks and 3 months after BPD. The retrospective part covered 23 patients who were examined after BPD for MO; the postoperative period was 4.7 [2.3; 7.2] years. A control group consisted of 22 healthy, normal weight volunteers. A 75-g oral glucose tolerance test was carried out in all the groups to study the levels of glucose, immunoreactive insulin (IRI), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon at 0, 30, 60, and 120 min. Results. T2DM patients showed improvement in glucose metabolism just 3 weeks after BPD; following 3 months, they had normalized fasting blood glucose levels (5.6 [5.0; 6.0] mmol/l). During 3 months, glycated hemoglobin decreased from 7.5 [6.6; 8.5] to 5.7 [5.3; 5.9]%. In the early period following BPD, there was an increase in basal and postprandial GLP-1 levels associated with the peak IRI concentration. In the late period after BPD, the enhanced secretion of IRI and GLP-1 persisted, which was followed by a reduction in postprandial glucose levels in 4 of the 23 patients. Conclusion. T2DM remission does not depend on weight loss in the early period after BPD. In this period, the significant improvement of glucose metabolic parameters in patients with obesity and T2DM is associated with elevated GLP-1 levels. The altered incretin response is a stable effect of BPD and remains in its late period.

2014 ◽  
Vol 11 (1) ◽  
pp. 24-31
Author(s):  
I I Dedov ◽  
G A Melnichenko ◽  
E A Troshina ◽  
N V Mazurina ◽  
N A Ogneva ◽  
...  

We’ve studied a carbohydrate metabolism in morbidly obese (MO) patients and the patients after bariatric surgery. The patients of the 1st group had BMI40 (n=22) and no history of diabetes mellitus. Patients after biliopancreatic diversion (BPD) performed for MO were included in the 2nd group (n=23). The 3rd group was a control group of normal weight healthy subjects (n=22). Blood glucose levels, insulin, GLP-1, GIP and glucagon during the OGTT (with 75 g of glucose) at 0, 30, 60 and 120 minutes were measured in all patients. In MO group fasting glucose levels were the highest. Impaired glucose metabolism was revealed in 68.2% of patients (n=10). Impaired fasting glucose (IFG) was diagnosed in 4 cases (18.2%), impaired glucose tolerance (IGT) in 11 patients (50%). In the BPD postprandial blood glucose levels (120 min) were lower if compared to the other groups. In 4 individuals (17.4%) we found postprandial hypoglycemia (2.8 mmol/l). Patients of the MO group had the highest fasting insulin levels and HOMA-IR (p0.001). The maximum of insulin concentration was seen on minute 30 of the OGTT in the 2nd and 3rd groups, and it was significantly higher in the post-bariatric patients (p=0.026). In MO group the maximum of the plasma insulin levels were on the 60th minute and were still elevated after 120 minutes. Fasting and stimulated (on the 30th minute) levels of GLP-1 were significantly higher after BPD (р=0.037 and p=0.022 at 0 and 30 min, respectively). Morbidly obese patients had higher fasting and stimulated GIP. Fasting glucagon concentrations were similar in the surgical and control groups, while the people with MO had higher initial levels of glucagon (p=0.013) and it was not suppressed during the OGTT (p=0.076). Glucose intolerance and insulin resistance incidence was higher in MO patients. Hyperglucagonemia, increased GIP and decreased GLP-1 levels are observed in MO patients. Stimulated plasma insulin and GLP-1 concentrations were significantly increased in patients who underwent BPD, and may cause postprandial hypoglycemia.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Qian Zhang ◽  
Xinhua Xiao ◽  
Ming Li ◽  
Wenhui Li ◽  
Miao Yu ◽  
...  

In China, TianMai Xiaoke tablet (TM) is used to treat type 2 diabetes. However, the exact mechanism of TM is not clear. This study is to investigate the effect of TM on glucose metabolism in diabetic rats and to identify whether TM takes a direct action through microRNAs on islet. Rats were divided into control group, diabetic group, low dose of TM group (TML), and high dose of TM group (TMH). Pancreas samples were analyzed using microRNA array and Q-PCR. Eight-week treatment with TM significantly decreased fasting blood glucose. The blood glucose was significantly reduced in TM-treated groups before and after oral glucose administration. Fasting insulin and HOMA-IR were suppressed in TM-treated groups. miR-448, let-7b, miR-540, miR-296, miR-880, miR-200a, miR-500, miR-10b, miR-336, miR-30d, miR-208, let-7e, miR-142-5p, miR-874, miR-375, miR-879, miR-501, and miR-188 were upregulated, while miR-301b, miR-134, and miR-652 were downregulated in TMH group. Through target gene analysis and real-time PCR verification, we found that these miRNAs, especially miR-375 and miR-30d, can stimulate insulin secretion in islet. Our data suggest that TM can improve blood glucose in diabetic rats which involved increasing the expression of miR-375 and miR-30d to activate insulin synthesis in islet.


2000 ◽  
Vol 83 (03) ◽  
pp. 475-479 ◽  
Author(s):  
Tomohiro Sakamoto ◽  
Hiroaki Kawano ◽  
Nobutaka Hirai ◽  
Shinzo Miyamoto ◽  
Keiji Takazoe ◽  
...  

SummaryWe examined the alteration of platelet aggregability in acute hyperglycemia during 75-gram oral glucose tolerance tests (OGTT). Twenty subjects underwent 75-gram OGTT and venous blood samples were obtained before (0 min), 60, 120 and 180 min postload. Platelet aggregability shown as the number of small platelet aggregates was measured with a novel laser-light scattering (LS) method. Platelet aggregability increased in parallel with both glucose and immunoreactive insulin (IRI) levels. The number of mean small aggregates at 60 min (12.30 ± 1.10 × 104) was significantly higher than the one at 0 min (8.32 ± 0.88 × 104, p <0.001), 120 min (10.63 ± 0.98 × 104, p <0.05) and 180 min (8.28 ± 0.84 × 104, p <0.001) (mean ± SEM). Small aggregates correlated positively with plasma glucose levels at 60 min postload (r = 0.67, p = 0.001) while not with IRI. It might be important to suppress transient hyperglycemia for preventing the onset of acute coronary syndromes that could be closely related to platelet hyperaggregability.


PHARMACON ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 160
Author(s):  
Adinda Fransisca Pongoh ◽  
Edwin De Queljoe ◽  
Henki Rotinsulu

ABSTRACT This study aims to determine the antidiabetic activity of papaya flower ethanol extract (Carica papaya L.) against male white rats (Rattus norvegicus) induced by alloxan. This research is experimental. Fifteen rats were divided into 5 treatment groups, each group consisted of 3 rats. The first group was the negative control group given Aquades, the second group was positive control given Glibenklamid, the three groups were 200 mg dose variation groups, four groups were 400 mg dose variations, and the five groups were 800 mg dose variations. Previously, rats were examined fasting blood glucose levels, then mice were induced by an alloxan dose of 120 mg / kgBW intraperitoneally. On the 3rd day blood glucose levels were examined and then treated according to groups for 7 days, measurement of blood glucose levels after the treatment was carried out once every 3 days namely day 3, day 7, and day 10. Data obtained were then analyzed statistically using SPSS , including normality test (Shapiro-Wilk), homogeneity test (Levene), ANOVA test (One way). The results of this study indicate that Papaya Flower (Carica papaya L.) Ethanol Extract can provide the best blood glucose level reduction effect at a dose of 800 mg. Keywords : Antidiabetic, Papaya Flower Extract (Carica papaya L.), Diabettes Mellitus, Male White Rat (Rattus norvegicus), Aloxan.  ABSTRAK Penelitian ini bertujuan untuk mengetahui efektivitas Antidiabetik Ekstrak Etanol Bunga Pepaya (Carica papaya L.) Terhadap Tikus Putih Jantan (Rattus norvegicus) Yang Diinduksi Aloksan. Penelitian ini bersifat eksperimental. Sebanyak 15 ekor tikus dibagi ke dalam 5 kelompok perlakuan masing- masing kelompok terdiri dari 3 ekor tikus. Kelompok pertama kelompok Kontrol negatif yang diberikan Aquades, Kelompok kedua Kontrol Positif yang diberikan Glibenklamid, kelompok tiga kelompok variasi dosis 200 mg, kelompok empat kelompok variasi dosis 400 mg, dan kelompok lima kelompok variasi dosis 800 mg. Sebelumnya tikus dilakukan pemeriksaan kadar glukosa darah puasa, selanjutnya tikus diinduksi Aloksan dosis 120 mg/kgBB secara intraperitoneal. Pada hari ke 3 diperiksa kadar Glukosa darah kemudian diberikan perlakuan sesuai kelompok selama 7 hari, pengukuran kadar glukosa darah setelah perlakuan dilakukan 3 hari sekali yaitu hari ke 3, hari ke 7, dan hari ke 10. Data yang diperoleh kemudian dianalisis secara statistik menggunakan SPSS, meliputi uji normalitas (Shapiro-Wilk), uji homogenitas (Levene), uji ANOVA (One way). Hasil penelitian ini menunjukkan bahwa Ekstrak Etanol Bunga Pepaya (Carica papaya L.)  dapat memberikan efek penurunan kadar glukosa darah yang paling baik yaitu pada dosis 800 mg. Kata kunci : Antidiabetik, Ekstrak Bunga pepaya (Carica papaya L.), Diabettes Mellitus, TikusPutih Jantan (Rattus norvegicus), Aloksan.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Chadakarn Phaloprakarn ◽  
Siriwan Tangjitgamol

Abstract Background Blood glucose levels during pregnancy may reflect the severity of insulin secretory defects and/or insulin resistance during gestational diabetes mellitus (GDM) pregnancy. We hypothesized that suboptimal glycemic control in women with GDM could increase the risk of postpartum type 2 diabetes mellitus (T2DM) or prediabetes. Our objective was to evaluate the impact of plasma glucose levels throughout GDM pregnancy on the risk of postpartum T2DM or prediabetes. Methods The medical records of 706 women with GDM who underwent a postpartum 75-g, 2-hour oral glucose tolerance test at our institution between January 2011 and December 2018 were reviewed. These women were classified into 2 groups according to glycemic control during pregnancy: ≤ 1 occasion of either fasting glucose ≥ 95 mg/dL or 2-hour postprandial glucose ≥ 120 mg/dL was defined as optimal glycemic control or else was classified as suboptimal glycemic control. Rates of postpartum T2DM and prediabetes were compared between women with optimal (n = 505) and suboptimal (n = 201) glycemic control. Results The rates of postpartum T2DM and prediabetes were significantly higher in the suboptimal glycemic control group than in the optimal glycemic control group: 22.4% vs. 3.0%, P < 0.001 for T2DM and 45.3% vs. 23.5%, P < 0.001 for prediabetes. In a multivariate analysis, suboptimal glucose control during pregnancy was an independent risk factor for developing either postpartum T2DM or prediabetes. The adjusted odds ratios were 8.4 (95% confidence interval, 3.5–20.3) for T2DM and 3.9 (95% confidence interval, 2.5–6.1) for prediabetes. Conclusion Our findings suggest that blood glucose levels during GDM pregnancy have an impact on the risk of postpartum T2DM and prediabetes.


2019 ◽  
Vol 9 (1) ◽  
pp. 86 ◽  
Author(s):  
Zulkarni Zulkarni

This Research was conducted to determine the effect of ethanol extract from red chilli (Capsicum annuum L)in lowering blood glucose levels of hyperglycemic male white mices. This study used 30 malewhitemices and divided into 6 groups: negative control group, the positive control group, the treatmentgroup withdosage of 200 mg / kgweight, 400 mg / kgwieght, 600 mg / kg weight and a comparison group with glibenclamide with dosage of 5 mg / kgweightadministered orally for 21 days. The level of fasting blood glucose was checked 6 days after dexamethasone induced, and after the ethanol extract of red chilies on day 7th, 14th, and 21st. The data was analyzed statistically with one –way and two-way Anova by usingSPSS16 program and proceed with the test Duncan to look the significant difference between treatments. The results showed that the ethanol extract from red chilies with a dosage of 200mg / kgweight, 400mg / kgweight, 600 mg / kgweight showed the effect in lowering blood sugar levels in male white mices hyperglycemia significantly (p <0.05). The duration ethanol extract of red chili affected blood glucose levels. The most effective duration in lowering blood glucose levels is the administration of a preparation within 21 days.


Author(s):  
Kamadyaapa Davie Rexon ◽  
Gondwe Mavuto Masopera ◽  
Shauli Mathulo ◽  
Sewani Rusike Constance ◽  
Nkeh Chungag Benedicta

  Objective: This study was conducted to scientifically evaluate the antidiabetic and antioxidant effects of ethanolic leaf extract of Erythrina abbysinica (EEA).Methods: Acute and sub-chronic effects of EEA at 100, 200, and 400 mg/kg/bwt and glibenclamide (GL) at 5 mg/kg/bwt. were evaluated in both normal and streptozotocin (STZ)-induced diabetic male Wistar rats (250–300 g). The acute studies were performed using oral glucose tolerance test (OGTT). In sub-chronic studies, animals were orally administered with EEA and GL daily for 6 w. Brine shrimp assay was used to determine the toxicity of EEA. 1, 1-diphenyl-2-picrylhydrazyl, ferric reducing capacity of plasma, and thiobarbituric acid reactive substances assays were used to determine antioxidant properties of EEA.Results: Following OGTT, EEA significantly (p<0.05) and dose-dependently (100, 200, and 400 mg/kg/bwt) decreased blood glucose levels in both normal and STZ-induced diabetic rats when compared with positive and negative control counterparts at all-time points, whereas GL significantly (p<0.05) decreased blood glucose only in normal rats but not in diabetic rats. Daily, oral administration of EEA for 6 w significantly (p<0.05) and dose-dependently (100, 200, and 400 mg/kg/bwt) decreased blood glucose levels in STZ-induced diabetic rats when compared with the diabetic control group. EEA revealed weak toxicity with a lethal concentration50 value of 997 μg/ml). Furthermore, EEA showed significant free radical scavenging, total antioxidant, and anti-lipid peroxidative capacities.Conclusion: The study has shed more light on the scientific basis for the use of E. abbysinica in management of diabetes in some communities of Eastern Cape of South Africa.


2019 ◽  
Vol 316 (3) ◽  
pp. E397-E409
Author(s):  
Maigen Bethea ◽  
Yanping Liu ◽  
Alexa K. Wade ◽  
Rachel Mullen ◽  
Rajesh Gupta ◽  
...  

The LIM-homeodomain (LIM-HD) transcription factor Islet-1 (Isl1) interacts with the LIM domain-binding protein 1 (Ldb1) coregulator to control expression of key pancreatic β-cell genes. However, Ldb1 also has Isl1-independent effects, supporting that another LIM-HD factor interacts with Ldb1 to impact β-cell development and/or function. LIM homeobox 1 (Lhx1) is an Isl1-related LIM-HD transcription factor that appears to be expressed in the developing mouse pancreas and in adult islets. However, roles for this factor in the pancreas are unknown. This study aimed to determine Lhx1 interactions and elucidate gene regulatory and physiological roles in the pancreas. Co-immunoprecipitation using β-cell extracts demonstrated an interaction between Lhx1 and Isl1, and thus we hypothesized that Lhx1 and Isl1 regulate similar target genes. To test this, we employed siRNA-mediated Lhx1 knockdown in β-cell lines and discovered reduced Glp1R mRNA. Chromatin immunoprecipitation revealed Lhx1 occupancy at a domain also known to be occupied by Isl1 and Ldb1. Through development of a pancreas-wide knockout mouse model ( Lhx1∆Panc), we demonstrate that aged Lhx1∆Panc mice have elevated fasting blood glucose levels, altered intraperitoneal and oral glucose tolerance, and significantly upregulated glucagon, somatostatin, pancreatic polypeptide, MafB, and Arx islet mRNAs. Additionally, Lhx1∆Panc mice exhibit significantly reduced Glp1R, an mRNA encoding the insulinotropic receptor for glucagon-like peptide 1 along with a concomitant dampened Glp1 response and mild glucose intolerance in mice challenged with oral glucose. These data are the first to reveal that the Lhx1 transcription factor contributes to normal glucose homeostasis and Glp1 responses.


2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Gergő Szűcs ◽  
Andrea Sója ◽  
Mária Péter ◽  
Márta Sárközy ◽  
Bella Bruszel ◽  
...  

Prediabetes is a condition affecting more than 35% of the population. In some forms, excessive carbohydrate intake (primarily refined sugar) plays a prominent role. Prediabetes is a symptomless, mostly unrecognized disease which increases cardiovascular risk. In our work, we examined the effect of a fructose-enriched diet on cardiac function and lipidome as well as proteome of cardiac muscle. Male Wistar rats were divided into two groups. The control group received a normal diet while the fructose-fed group received 60% fructose-supplemented chow for 24 weeks. Fasting blood glucose measurement and oral glucose tolerance test (OGTT) showed slightly but significantly elevated values due to fructose feeding indicating development of a prediabetic condition. Both echocardiography and isolated working heart perfusion performed at the end of the feeding protocol demonstrated diastolic cardiac dysfunction in the fructose-fed group. Mass spectrometry-based, high-performance lipidomic and proteomic analyses were executed from cardiac tissue. The lipidomic analysis revealed complex rearrangement of the whole lipidome with special emphasis on defects in cardiolipin remodeling. The proteomic analysis showed significant changes in 75 cardiac proteins due to fructose feeding including mitochondria-, apoptosis-, and oxidative stress-related proteins. Nevertheless, just very weak or no signs of apoptosis induction and oxidative stress were detected in the hearts of fructose-fed rats. Our results suggest that fructose feeding induces marked alterations in the cardiac lipidome, especially in cardiolipin remodeling, which leads to mitochondrial dysfunction and impaired cardiac function. However, at the same time, several adaptive responses are induced at the proteome level in order to maintain a homeostatic balance. These findings demonstrate that even very early stages of prediabetes can impair cardiac function and can result in significant changes in the lipidome and proteome of the heart prior to the development of excessive oxidative stress and cell damage.


2007 ◽  
Vol 92 (3) ◽  
pp. 1172-1175 ◽  
Author(s):  
Mogher Khamaisi ◽  
Eran Regev ◽  
Noam Yarom ◽  
Batia Avni ◽  
Eran Leitersdorf ◽  
...  

Abstract Context: Bisphosphonate-related osteonecrosis (BON) of the jaws is a newly identified condition for which the exact mechanism involved in its pathogenesis remains obscure. Objective: The objective of the study was to evaluate whether diabetes mellitus (DM) may be a contributing factor in the development of BON. Design: From 2004 to 2006, 31 patients were diagnosed with BON. The diagnosis of BON was based on the medical and dental history of each patient as well as the observation of clinical signs and symptoms of this pathological process. DM was based on two consecutive fasting blood glucose levels above 7 mmol/liter. Setting: The study was completed in the Hebrew University-Hadassah Hospital referral center. Results: Of the 31 patients with BON, 18 (58%) were found to have DM or impaired fasting glucose. The proportion of diabetic patients was much higher than expected relative to the incidence of DM in the general population (14%) and compared with the proportion of diabetic patients in a control group of oncological patients treated with bisphosphonates and without BON (12%) (P = 0.00003). Conclusions: This finding indicates that DM may be a risk factor for BON and that DM patients treated with bisphosphonates should be carefully monitored. We discuss here the bone metabolic pathways characteristic of DM patients and the way in which these pathways can augment the effects of bisphosphonates.


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