scholarly journals β-Cell Insulin Secretory Response to Oral Hypoglycemic Agents Is Blunted in Humansin Vivoduring Moderate Hypoglycemia

2004 ◽  
Vol 89 (9) ◽  
pp. 4553-4557 ◽  
Author(s):  
Waleed Aldhahi ◽  
Jen Armstrong ◽  
Clara Bouche ◽  
Richard D. Carr ◽  
Alan Moses ◽  
...  
Keyword(s):  
Secretory Response ◽  
Hypoglycemic Agents ◽  
Oral Hypoglycemic Agents ◽  
Β Cell ◽  
Insulin Secretory Response

THE EFFECT OF FASTING AND SELECTIVE RE-FEEDING ON INSULIN RELEASE IN THE RAT

1973 ◽  
Vol 72 (1) ◽  
pp. 46-53 ◽  
Author(s):  
D. S. Turner ◽  
D. A. B. Young
Keyword(s):  
Insulin Release ◽  
Acute Effect ◽  
Secretory Response ◽  
Release Mechanism ◽  
Β Cell ◽  
Intestinal Hormones ◽  
Intravenous Glucose ◽  
Glucose Ingestion ◽  
Glucose Test ◽  
Insulin Secretory Response

ABSTRACT The insulin secretory response in the rat to intravenous glucose was found to be greatly impaired by fasting for three days, whereas that to orally administered glucose was not significantly affected. Rats fasted for two days were given either protein or starch pellets for six hours, and then fasted for a further eighteen hours before the intravenous glucose test. The protein pre-feeding failed to affect significantly the subsequent insulin secretory response to intravenous glucose, whereas starch prefeeding greatly enhanced it. It is suggested that intestinal hormones released by glucose ingestion may exert not only an acute effect on insulin release, but also a 'priming' effect on the insulin release mechanism of the β cell, which enables it to respond to the subsequent stimulus of glucose alone.

Abnormal Insulin Secretory Response to Food after Acute Hypoglycaemia in Man: Evidence for β-Cell Glucopenia

1980 ◽  
Vol 59 (3) ◽  
pp. 16P-16P
Author(s):  
R. J. M. Corrall ◽  
B. M. Frier ◽  
J. P. Ashby ◽  
T. E. Adrian ◽  
S. R. Bloom
Keyword(s):  
Secretory Response ◽  
Β Cell ◽  
Insulin Secretory Response

scholarly journals Inhibition of calpain blocks pancreatic β-cell spreading and insulin secretion

2005 ◽  
Vol 289 (2) ◽  
pp. E313-E321 ◽  
Author(s):  
Géraldine Parnaud ◽  
Eva Hammar ◽  
Dominique G. Rouiller ◽  
Domenico Bosco
Keyword(s):  
Insulin Secretion ◽  
Cell Attachment ◽  
Cell Spreading ◽  
Cysteine Proteases ◽  
Secretory Response ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Insulin Secretory Response ◽  
Calpain Inhibitors

In addition to promoting insulin secretion, an increase in cytosolic Ca2+ triggered by glucose has been shown to be crucial for spreading of β-cells attached on extracellular matrix (804G matrix). Calpains are Ca2+-dependent cysteine proteases involved in an extended spectrum of cellular responses, including cytoskeletal rearrangements and vesicular trafficking. The present work aimed to assess whether calpain is also implicated in the process of Ca2+-induced insulin secretion and spreading of rat pancreatic β-cells. The results indicate calpain dependency of β-cell spreading on 804G matrix. Indeed, treatment with three distinct calpain inhibitors (N-Ac-Leu-Leu-norleucinal, calpeptin, and ethyl(+)-(2S,3S)-3-[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butyl-carbamoyl]-2-ox-iranecarboxylate) inhibited cell spreading induced by glucose and KCl, whereas cell attachment was not significantly modified. Calpain inhibitors also suppressed glucose- and KCl-stimulated insulin secretion without affecting insulin synthesis. Washing the inhibitor out of the cell culture restored spreading on 804G matrix and insulin secretory response after 24 h. In addition, incubation with calpeptin did not affect insulin secretory response to mastoparan that acts on exocytosis downstream of intracellular calcium [Ca2+]i. Finally, calpeptin was shown to affect the [Ca2+]i response to glucose but not to KCl. In summary, the results show that inhibition of calpain blocks spreading and insulin secretion of primary pancreatic β-cells. It is therefore suggested that calpain could be a mediator of Ca2+-induced-insulin secretion and β-cell spreading.

scholarly journals Linearity of β-cell response across the metabolic spectrum and to pharmacology: insights from a graded glucose infusion-based investigation series

2016 ◽  
Vol 310 (11) ◽  
pp. E865-E873 ◽  
Author(s):  
Sudha S. Shankar ◽  
R. Ravi Shankar ◽  
Lori A. Mixson ◽  
Deborah L. Miller ◽  
Christopher Chung ◽  
...  
Keyword(s):  
Cell Function ◽  
Secretory Response ◽  
Glucose Infusion ◽  
Response Patterns ◽  
Β Cell ◽  
Clinical Trial Registration ◽  
Hyperglycemic Clamp ◽  
Insulin Secretagogues ◽  
Insulin Secretory Response

The graded glucose infusion (GGI) examines insulin secretory response patterns to continuously escalating glycemia. The current study series sought to more fully appraise its performance characteristics. Key questions addressed were comparison of the GGI to the hyperglycemic clamp (HGC), comparison of insulin secretory response patterns across three volunteer populations known to differ in β-cell function (healthy nonobese, obese nondiabetic, and type 2 diabetic), and characterization of effects of known insulin secretagogues in the context of a GGI. Insulin secretory response was measured as changes in insulin, C-peptide, insulin secretion rates (ISR), and ratio of ISR to prevailing glucose (ISR/G). The GGI correlated well with the HGC ( r = 0.72 for ISR/G, P < 0.01). The insulin secretory response in type 2 diabetes (T2DM) was significantly blunted ( P < 0.001), whereas it was significantly increased in obese nondiabetics compared with healthy nonobese ( P < 0.001). Finally, robust ( P < 0.001 over placebo) pharmacological effects were observed in T2DM and healthy nonobese volunteers. Collectively, the findings of this investigational series bolster confidence that the GGI has solid attributes for assessing insulin secretory response to glucose across populations and pharmacology. Notably, the coupling of insulin secretory response to glycemic changes was distinctly and uniformly linear across populations and in the context of insulin secretagogues. (Clinical Trial Registration Nos. NCT00782418, NCT01055340, NCT01373450)

Real-World Clinical Effectiveness and Tolerability of Hydroxychloroquine 400 Mg in Uncontrolled Type 2 Diabetes Subjects who are not Willing to Initiate Insulin Therapy (HYQ-Real-World Study)

2019 ◽  
Vol 15 (6) ◽  
pp. 510-519 ◽  
Author(s):  
Amit Gupta
Keyword(s):  
Body Weight ◽  
Glycemic Control ◽  
Insulin Therapy ◽  
Real World ◽  
Antidiabetic Drugs ◽  
Hypoglycemic Agents ◽  
Oral Hypoglycemic Agents ◽  
Good Glycemic Control ◽  
Hs Crp ◽  
Change In Mean

Objective: The epidemic of T2DM is rising across the globe. Systemic inflammation plays a pivotal role in the pathogenesis and complications of T2DM. Combination of two or more oral hypoglycemic agents (OHA) is widely prescribed in patients with T2DM, however many patients have poor glycemic control despite receiving combination therapy. The new antidiabetic drugs are relatively costly or many patients have anxiety over the use of injectable insulin. The objective of this observational study was to investigate the effectiveness and tolerability of hydroxychloroquine (HCQ) in T2DM patients uncontrolled on multiple OHA and despite high sugar level not willing to initiate insulin therapy in a real-world clinical setting. Methods: A prospective, investigator-initiated, observational, single-centred study was conducted where 250 patients (18-65 years) with T2DM for more than 5 years, with uncontrolled glycemia despite on a combination of multiple OHA, HbA1c between ≥7% and <10.5%, FPG >130 mg/dL or PPG >180 mg/dL and BMI between >25 and <39 kg/m2, were prescribed hydroxychloroquine sulphate 400 mg once daily for 48 weeks. Percentage of drugs used at the baseline were as follows: metformin 2000 mg (100%), glimepiride 4 mg (100%), pioglitazone 30 mg (100%), sitagliptin 100 mg (100%), canagliflozin 300 mg (52.4%), empagliflozin 25 mg (22.8%), dapagliflozin 10 mg (17.6%) and voglibose 0.3 mg (62%). Mean change in HbA1c, blood glucose and hs-CRP at baseline, week 12, 24 and 48 were assessed using the paired t-test. Results: After 48 weeks of add-on treatment with HCQ, almost all SGLT-2 inhibitors were withdrawn; metformin dose was reduced to 1000 mg, glimepiride reduced to 1 mg and sitagliptin reduced to 50 mg OD. Patients continued to have good glycemic control. HbA1c was reduced from 8.83% to 6.44%. Reduction in FPG was 40.78% (baseline 177.30 mg/dL) and PPG was reduced by 58.95% (baseline 329.86 mg/dL). Change in mean body weight was -4.66 Kg. The reduction in glycemic parameters and mean body weight was significant (p < 0.0001). Hs-CRP was significantly reduced from 2.70±1.98 mg/L to 0.71±0.30 mg/L 9 (p < 0.0001). More reduction in glycemic parameters and body weight was observed among the patients with higher hs-CRP (> 3 mg/L) as compared to patients with baseline hs- CRP ≤ 3 mg/L. Most common adverse events reported with the drug therapy were GI irritation (3.6%) and hypoglycemia (2%). None of the patients required medical assistance for hypoglycemia. Conclusion: Add-on treatment of HCQ effectively improved glycemic control in T2DM patients uncontrolled on multiple antidiabetic drugs. By virtue of its antidiabetic and anti-inflammatory properties, it may emerge as a valuable therapeutic intervention for the patients with T2DM.

Phenanthridine Sulfonamide Derivatives as Potential DPP-IV Inhibitors: Design, Synthesis and Biological Evaluation

2020 ◽  
Vol 16 ◽  
Author(s):  
Reema Abu Khalaf ◽  
Shorooq Alqazaqi ◽  
Maram Aburezeq ◽  
Dima Sabbah ◽  
Ghadeer Albadawi ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Biological Evaluation ◽  
Ligand Docking ◽  
Biological Assessment ◽  
Hypoglycemic Agents ◽  
Binding Affinities ◽  
Oral Hypoglycemic Agents ◽  
Design Synthesis ◽  
Dpp Iv

Background: Diabetes mellitus is a chronic metabolic disorder, characterized by hyperglycemia over a prolonged period, disturbance of fat, protein and carbohydrate metabolism, resulting from defective insulin secretion, insulin action or both. Dipeptidyl peptidase-IV (DPP-IV) inhibitors are relatively a new class of oral hypoglycemic agents that reduces the deterioration of gut-derived endogenous incretin hormones that are secreted in response to food ingestion to stimulate the secretion of insulin from beta cells of pancreas. Objective: In this study, synthesis, characterization, and biological assessment of twelve novel phenanthridine sulfonamide derivatives 3a-3l as potential DPP-IV inhibitors was carried out. The target compounds were docked to study the molecular interactions and binding affinities against DPP-IV enzyme. Methods: The synthesized molecules were characterized using 1H-NMR, 13C-NMR, IR, and MS. Quantum-polarized ligand docking (QPLD) was also performed. Results: In vitro biological evaluation of compounds 3a-3l reveals comparable DPP-IV inhibitory activities ranging from 10%-46% at 100 µM concentration, where compound 3d harboring ortho-fluoro moiety exhibited the highest inhibitory activity. QPLD study shows that compounds 3a-3l accommodate DPP-IV binding site and form H-bonding with the R125, E205, E206, S209, F357, R358, K554, W629, S630, Y631, Y662, R669 and Y752 backbones. Conclusion: In conclusion, phenanthridine sulfonamides could serve as potential DPP-IV inhibitors that require further structural optimization in order to enhance their inhibitory activity.

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