scholarly journals Glucagon receptor antagonist upregulates circulating GLP-1 level by promoting intestinal L-cell proliferation and GLP-1 production in type 2 diabetes

2020 ◽  
Vol 8 (1) ◽  
pp. e001025 ◽  
Author(s):  
Shan Lang ◽  
Jin Yang ◽  
Kun Yang ◽  
Liangbiao Gu ◽  
Xiaona Cui ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Blood Glucose ◽  
Glycemic Control ◽  
Glucose Tolerance ◽  
Cell Number ◽  
Glucagon Receptor ◽  
L Cell ◽  
Primary Mouse ◽  
Gut Length

ObjectiveGlucagon receptor (GCGR) blockage improves glycemic control and increases circulating glucagon-like peptide-1 (GLP-1) level in diabetic animals and humans. The elevated GLP-1 has been reported to be involved in the hypoglycemic effect of GCGR blockage. However, the source of this elevation remains to be clarified.Research design and methodsREMD 2.59, a human GCGR monoclonal antibody (mAb), was administrated for 12 weeks in db/db mice and high-fat diet+streptozotocin (HFD/STZ)-induced type 2 diabetic (T2D) mice. Blood glucose, glucose tolerance and plasma GLP-1 were evaluated during the treatment. The gut length, epithelial area, and L-cell number and proliferation were detected after the mice were sacrificed. Cell proliferation and GLP-1 production were measured in mouse L-cell line GLUTag cells, and primary mouse and human enterocytes. Moreover, GLP-1 receptor (GLP-1R) antagonist or protein kinase A (PKA) inhibitor was used in GLUTag cells to determine the involved signaling pathways.ResultsTreatment with the GCGR mAb lowered blood glucose level, improved glucose tolerance and elevated plasma GLP-1 level in both db/db and HFD/STZ-induced T2D mice. Besides, the treatment promoted L-cell proliferation and LK-cell expansion, and increased the gut length, epithelial area and L-cell number in these two T2D mice. Similarly, our in vitro study showed that the GCGR mAb promoted L-cell proliferation and increased GLP-1 production in GLUTag cells, and primary mouse and human enterocytes. Furthermore, either GLP-1R antagonist or PKA inhibitor diminished the effects of GCGR mAb on L-cell proliferation and GLP-1 production.ConclusionsThe elevated circulating GLP-1 level by GCGR mAb is mainly due to intestinal L-cell proliferation and GLP-1 production, which may be mediated via GLP-1R/PKA signaling pathways. Therefore, GCGR mAb represents a promising strategy to improve glycemic control and restore the impaired GLP-1 production in T2D.

scholarly journals Long-term hyperglucagonaemia induces early metabolic and renal phenotypes of Type 2 diabetes in mice

2008 ◽  
Vol 114 (9) ◽  
pp. 591-601 ◽  
Author(s):  
Xiao C. Li ◽  
Tang-dong Liao ◽  
Jia L. Zhuo
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Weight Ratio ◽  
Glomerular Injury ◽  
Glucagon Receptor

Clinical studies have shown that patients with early Type 2 diabetes often have elevated serum glucagon rather than insulin deficiency. Imbalance of insulin and glucagon in favouring the latter may contribute to impaired glucose tolerance, persistent hyperglycaemia, microalbuminuria and glomerular injury. In the present study, we tested the hypothesis that long-term glucagon infusion induces early metabolic and renal phenotypes of Type 2 diabetes in mice by activating glucagon receptors. Five groups of adult male C57BL/6J mice were treated with vehicle, glucagon alone (1 μg/h via an osmotic minipump, intraperitoneally), glucagon plus the glucagon receptor antagonist [Des-His1-Glu9]glucagon (5 μg/h via an osmotic minipump), [Des-His1-Glu9]glucagon alone or a high glucose load alone (2% glucose in the drinking water) for 4 weeks. Glucagon infusion increased serum glucagon by 129% (P<0.05), raised systolic BP (blood pressure) by 21 mmHg (P<0.01), elevated fasting blood glucose by 42% (P<0.01), impaired glucose tolerance (P<0.01), increased the kidney weight/body weight ratio (P<0.05) and 24 h urinary albumin excretion by 108% (P<0.01) and induced glomerular mesangial expansion and extracellular matrix deposition. These responses were associated with marked increases in phosphorylated ERK1/2 (extracellular-signal-regulated kinase 1/2) and Akt signalling proteins in the liver and kidney (P<0.01). Serum insulin did not increase proportionally. Concurrent administration of [Des-His1-Glu9]glucagon with glucagon significantly attenuated glucagon-increased BP, fasting blood glucose, kidney weight/body weight ratio and 24 h urinary albumin excretion. [Des-His1-Glu9]glucagon also improved glucagon-inpaired glucose tolerance, increased serum insulin by 56% (P<0.05) and attenuated glomerular injury. However, [Des-His1-Glu9]glucagon or high glucose administration alone did not elevate fasting blood glucose levels, impair glucose tolerance or induce renal injury. These results demonstrate for the first time that long-term hyperglucagonaemia in mice induces early metabolic and renal phenotypes of Type 2 diabetes by activating glucagon receptors. This supports the idea that glucagon receptor blockade may be beneficial in treating insulin resistance and Type 2 diabetic renal complications.

scholarly journals Effect of Pseudocereal-Based Breakfast Meals on the First and Second Meal Glucose Tolerance in Healthy and Diabetic Subjects

2016 ◽  
Vol 4 (4) ◽  
pp. 565-573 ◽  
Author(s):  
Shreef G.N. Gabrial ◽  
Marie-Christine R. Shakib ◽  
Gamal N. Gabrial
Keyword(s):  
Blood Glucose ◽  
Glycemic Control ◽  
Glucose Tolerance ◽  
Glycemic Index ◽  
Healthy Subjects ◽  
Postprandial Blood Glucose ◽  
Glucose Response ◽  
Blood Glucose Response ◽  
Baseline Levels

BACKGROUND: Many studies have indicated that the incidence of serious diabetic complications may be reduced through strict glycemic control. A low glycemic index diet is one tool to improve insulin resistance and improve glycemic control in type 2 diabetes mellitus (T2DM).AIM: The objective was to study the effect of pseudocereals-based breakfasts (quinoa and buckwheat) on glucose variations at first meal (breakfast) and second meal (standardised lunch) in healthy and diabetic subjects.SUBJECTS AND METHODS: Twelve healthy subjects and 12 patients with Type 2 DM (not- insulin dependent) were recruited in the study. Subjects were provided with quinoa and buckwheat breakfast meals. A standardised lunch was provided 4 h after breakfast. Postprandial blood glucose response after breakfast and the second meal effect was measured in healthy and diabetic subjects. Incremental area under the curve (IAUC) values for glucose was measured in response to the breakfast and lunch. The glycemic index of the 2 pseudocereals-based test breakfasts was determined. A white wheat bread (WWB) was served as a reference breakfast meal.RESULTS: In post-breakfast analyses, healthy subjects showed that buckwheat meal had significantly lower IAUC values for blood glucose compared to WWB reference meal (P < 0.001) while quinoa meal showed no significance. In diabetic subjects, buckwheat and quinoa meals had significantly lower IAUC values for blood glucose compared to WWB reference meal (P < 0.001 and P < 0.05 respectively). Blood glucose concentrations started to decline gradually for the quinoa and buckwheat but not for WWB in all healthy and diabetic subjects and returned to near-fasting baseline levels by 210 min. Post-lunch analyses indicated higher IAUC for the two breakfast types in healthy and diabetic subjects. In addition, the quinoa and buckwheat breakfast meals were followed by a significantly flatter blood glucose response to the second meal for the period between 270 and 330 min. At the end of the second meal period, values were below or near-fasting baseline levels in the breakfast period. The blood glucose concentration after consuming quinoa meal showed a high peak at 30 min similar to that of WWB reference meal. This peak resulted in a high glycemic index (GI) for quinoa (89.4). The GI of buckwheat recorded a low value (26.8).CONCLUSION: The two studied pseudocereals; quinoa and buckwheat have high potential to improve glucose tolerance at the first and second meal (lunch) and are recommended to be introduced in our daily diet for healthy and diabetic subjects.

941-P: Frequency of Blood Glucose Monitoring in Relation to Medical Cost and Glycemic Control in Hospitalized Patients with Type 2 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 941-P
Author(s):  
LEI ZHANG ◽  
YAN GU ◽  
YUXIU YANG ◽  
NA WANG ◽  
WEIGUO GAO ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glycemic Control ◽  
Medical Cost ◽  
Glucose Monitoring ◽  
Hospitalized Patients ◽  
Blood Glucose Monitoring

scholarly journals Triangulating evidence for the causal impact of single-dose zinc supplement on glycemic control for type-2 diabetes

2021 ◽  
Author(s):  
Zhiyang Wang ◽  
Carine Ronsmans ◽  
Benjamin Woolf
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glycemic Control ◽  
Fasting Glucose ◽  
Causal Effect ◽  
Fasting Blood Glucose ◽  
Zinc Supplement ◽  
Diabetes Patients

Background: Although previous studies suggested the protective effect of zinc for type-2 diabetes, the unitary causal effect remains inconclusive. Objective: We investigated the causal effect of zinc as a single intervention on glycemic control in type-2 diabetes patients, using a systematic review of RCTs and two-sample Mendelian randomization (MR). Methods: Four outcomes were identified: fasting blood glucose/fasting glucose, hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), and serum insulin/fasting insulin level. In the systematic review, four databases were searched up to June 2021. Results were synthesized through the random-effects meta-analysis. Single nucleotide polymorphisms (SNPs) that are independent and are strongly related to zinc supplements were selected from MR-base to perform the two-sample MR with inverse-variance weighted (IVW) coefficient. Results: In the systematic review, 14 trials were included. The zinc supplement led to a significant reduction in the post-trial mean of fasting blood glucose (mean difference (MD): -26.52, 95%CI: -35.13, -17.91), HbA1C (MD: -0.52, 95%CI: -0.90, -0.13), and HOMA-IR (MD: -1.65, 95%CI: -2.62, -0.68), compared to the control group. In the two-sample MR, zinc supplement with 2 SNPs associated with lower fasting glucose (IVW coefficient: -2.04, 95%CI: -3.26, -0.83), but not specified type-2 diabetes. Conclusion: Although the study was limited by the few trials (review) and SNPs (two-sample MR), we demonstrated that the single zinc supplementary improved glycemic control among type-2 diabetes patients with causal evidence to a certain extent.

Self-Monitoring of Blood glucose(SMBG), Utilization of SMBG, Hypoglycemia Frequency and Glycemic Control in Type 2 Diabetes

2020 ◽  
Vol 32 (2) ◽  
pp. 51-60
Author(s):  
Minja Cho ◽  
Changkwan Lee ◽  
Eunjeong Lee ◽  
Miyoung Kim
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glycemic Control ◽  
Self Monitoring

Retinoic acid-induced proliferation of lung alveolar epithelial cells: relation with the IGF system

1998 ◽  
Vol 275 (1) ◽  
pp. L71-L79 ◽  
Author(s):  
Elodie Nabeyrat ◽  
Valérie Besnard ◽  
Sophie Corroyer ◽  
Véronique Cazals ◽  
Annick Clement
Keyword(s):  
Cell Proliferation ◽  
Retinoic Acid ◽  
Growth Factor ◽  
Alveolar Epithelium ◽  
Cell Number ◽  
Dependent Manner ◽  
Alveolar Epithelial ◽  
Igf System ◽  
Tgf Β1

Retinoids, including retinol and retinoic acid (RA) derivatives, are important molecules for lung growth and homeostasis. The presence of RA receptors and of RA-binding proteins in the alveolar epithelium led to suggest a role for RA on alveolar epithelial cell replication. In the present study, we examined the effects of RA on proliferation of the stem cells of the alveolar epithelium, the type 2 cells. We showed that treatment of serum-deprived type 2 cells with RA led to a stimulation of cell proliferation, with an increase in cell number in a dose-dependent manner. To gain some insights into the mechanisms involved, we studied the effects of RA on the expression of several components of the insulin-like growth factor (IGF) system that have been shown to be associated with the growth arrest of type 2 cells, mainly the IGF-binding protein-2 (IGFBP-2), IGF-II, and the type 2 IGF receptor. We documented a marked decrease in the expression of these components upon RA treatment. Using conditioned media from RA-treated cells, we provided evidence that the proliferative response of type 2 cells to RA was mediated through production of growth factor(s) distinct from IGF-I. We also showed that RA was able to reduce the decrease in cell number observed when type 2 cells were treated with transforming growth factor (TGF)-β1. These results together with the known stimulatory effect of TGF-β1 on IGFBP-2 expression led to suggest that RA may be associated with type 2 cell proliferation through mechanisms interfering with the TGF-β1 pathway.

scholarly journals Utilizing Technology-Enabled Intervention to Improve Blood Glucose Self-Management Outcome in Type 2 Diabetic Patients Initiated on Insulin Therapy: A Retrospective Real-World Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jian Lin ◽  
Xia Li ◽  
Shan Jiang ◽  
Xiao Ma ◽  
Yuxin Yang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glycemic Control ◽  
Insulin Therapy ◽  
Fasting Blood Glucose ◽  
Blood Glucose Control ◽  
Diabetic Patients ◽  
Premixed Insulin ◽  
Type 2 Diabetic Patients ◽  
Self Monitoring

Background. The aim of this study was to assess the benefits of a mobile-enabled app through Lilly Connected Care Program (LCCP) in achieving blood glucose control and adhering to self-monitoring of blood glucose in patients with type 2 diabetes mellitus (T2DM). Methods. This retrospective study included T2DM patients who were initiated on insulin therapy (mostly premixed insulin) after failure to respond to oral antidiabetic drugs. Patients were provided with glucometers enabled with synchronous data transmission to healthcare providers and family members. The primary objective was to assess the benefits of LCCP based on changes in fasting blood glucose (FBG) and postprandial glucose (PPG) levels from baseline to 12 weeks. Paired t-test was used to assess the change in blood glucose (BG) from baseline to week 12. Results. In total, 14,085 T2DM patients were recruited. Compared with baseline, significant reductions in FBG and PPG were evident at week 12 (FBG: -0.39 mmol/L; PPG: −0.79 mmol/L; both P < 0.001 ). Furthermore, at week 12, the proportion of patients attaining a target glucose level of FBG <7.0 mmol/L and PPG <10.0 mmol/L was 25.37% and 59.68%, respectively, with a statistically significant increase compared with that at baseline (6.74% and 45.59%, respectively, both P < 0.001 ). The frequent monitoring of patients could gain a higher target achievement of FBG (28.1% vs 24.2%) and PPG (64.4% vs 55.1%) than the occasional monitoring patients. Additionally, the incidence of hypoglycemia gradually decreased and was significantly lower than the baseline level. Conclusions. In T2DM patients with poor glycemic control, the application of mobile enabled intervention (LCCP) along with insulin significantly reduced the hypoglycemia while improving glycemic control during period of naïve initiating insulin therapy. Additionally, the high frequency of BG self-monitoring was associated with better glycemic control.

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