scholarly journals Deciphering the Hypoglycemic Glucagon Response: Development of a Graded Hyperinsulinemic Hypoglycemic Clamp Technique in Female Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3866-3871 ◽  
Author(s):  
Siri Malmgren ◽  
Bo Ahrén
Keyword(s):  
Blood Glucose ◽  
Defense Mechanisms ◽  
Tolerance Test ◽  
Glucose Lowering ◽  
Insulin Tolerance ◽  
Hyperbolic Curve ◽  
Glucose Lowering Therapy

Glucose lowering therapy in type 1 and type 2 diabetes is often associated with hypoglycemic events. To avoid this, glucose lowering therapies need to be developed that support the hypoglycemic defense mechanisms. Such development needs a tool for evaluating counterregulatory mechanisms in vivo. A sustained glucagon release during hypoglycemia is of most importance to hypoglycemic defense mechanisms. We have therefore developed a graded hyperinsulinemic hypoglycemic clamp in mice and used it to evaluate counterregulatory glucagon dynamics. Glucose was clamped at narrow intervals aiming at 2.5, 3.5, 4.5, and 6.0 mmol/L. Glucagon levels were increased during hypoglycemia in a glucose-dependent way with a glucagon counterregulatory threshold between 3.5 and 4.0 mmol/L. Modelling the glucose-glucagon relationship using a hyperbolic curve with the equation: plasma glucagon = −4.20 + 90.79/blood glucose showed high correlation. When comparing this method to the insulin tolerance test as an approach to study glucagon dynamics in vivo, we found that the graded clamp more efficiently evoked a robust, predictable, glucagon response with considerably less variation in blood glucose. In conclusion, we have developed a tool for the study of in vivo glucagon dynamics during hypoglycemia in mice and demonstrated a hyperbolic glucose-counterregulatory glucagon relationship.

Sulfonylureas in today’s blood glucose lowering therapy.New data on advantages and potential barriers of an “old” antidiabetic group

2015 ◽  
Vol 156 (13) ◽  
pp. 511-515
Author(s):  
Gábor Winkler
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 ◽  
Sulfonylurea Compounds ◽  
Drug Of Choice ◽  
Antidiabetic Treatment ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucose Lowering Therapy

Sulfonylurea compounds have been basic elements of antidiabetic treatment in type 2 diabetes for a long time. However, with the introduction of incretin type insulin secretagogues it is often arises, whether is still there a place for sulfonylureas in the today’s therapy. To answer this question the author overviews general pharmaceutical characteristics of the sulfonylurea compounds as well as individual particularities of the second generation derivatives used at present in Hungary. The author details also the most important differences between incretin type drugs − first of all dipeptidyl peptidase-4 inhibitors − and sulfonylureas. On the basis of available data it can be concluded in accordance with the latest international guidelines, that sulfonylureas have still role in the blood glucose lowering therapy of type 2 diabetes, though they became somewhat pushed back among insulin secretagogue type drugs. If a sulfonylurea compound is the drug of choice, it is important to select the appropriate molecule (in case of normal renal function gliclazide or glimepiride). It is also important to re-educate the patient, as well as to apply the minimal dose providing the desired glycaemic effect. Orv. Hetil., 2015, 156(13), 511–515.

scholarly journals Glucose-Lowering Therapy in Patients With Postpancreatitis Diabetes Mellitus: A Nationwide Population-Based Cohort Study

2021 ◽  
Author(s):  
Rikke Viggers ◽  
Morten Hasselstrøm Jensen ◽  
Henrik Vitus Bering Laursen ◽  
Asbjørn Mohr Drewes ◽  
Peter Vestergaard ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Diabetes Incidence ◽  
Secondary Diabetes ◽  
Glucose Lowering ◽  
Lowering Therapy ◽  
Glucose Lowering Therapy

<p><i>Objective</i>: Postpancreatitis diabetes mellitus (PPDM) is a type of secondary diabetes that requires special considerations for management. The main objective was to examine prescription patterns of glucose-lowering therapy among adults with PPDM compared to type 1 and type 2 diabetes.</p> <p><i>Research Design and Methods:</i> In a Danish nation-wide population-based cohort study we identified all individuals with adult-onset diabetes mellitus in the period 2000-2018 and categorized them as type 1 diabetes, type 2 diabetes or PPDM. We ascertained diabetes incidence rates, clinical and demographic characteristics, classifications and prescription patterns of glucose-lowering therapy and compared these parameters across diabetes subgroups. </p> <p><i>Results</i><i>:</i> Among 398,456 adults with new-onset diabetes mellitus, 5,879 (1.5%) had PPDM, 9,252 (2.3%) type 1 diabetes and the remaining type 2 diabetes (96.2%). The incidence rate of PPDM was 7.9 (95% CI 7.7-8.1) per 100,000 person-years vs. 12.5 (95% CI 12.2-12.7) for type 1 diabetes (incidence-rate-ratio 0.6; 95% CI 0.6-0.7, p<0.001). A sizeable proportion of PPDM patients were classified as type 2 diabetes (44.9%) and were prescribed sulfonylureas (25.2%) and incretin-based therapies (18.0%) that can potentially be harmful in PPDM. In contrast, 35.0% of patients never received biguanides, which are associated with a survival benefit in PPDM. Increased insulin requirements were observed for patients with PPDM compared to type 2 diabetes (hazard ratio 3.10; 95% CI 2.96-3.23, p<0.001) in particular for PPDM associated with chronic pancreatitis (hazard ratio 4.30; 95% CI 4.01-4.56, p<0.001).</p> <p><i>Conclusions</i><i>:</i> PPDM is a common type of secondary diabetes in adults but is often misclassified and treated as type 2 diabetes, although PPDM requires special considerations for management.</p>

scholarly journals Glucose-Lowering Therapy in Patients With Postpancreatitis Diabetes Mellitus: A Nationwide Population-Based Cohort Study

2021 ◽  
Author(s):  
Rikke Viggers ◽  
Morten Hasselstrøm Jensen ◽  
Henrik Vitus Bering Laursen ◽  
Asbjørn Mohr Drewes ◽  
Peter Vestergaard ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Diabetes Incidence ◽  
Secondary Diabetes ◽  
Glucose Lowering ◽  
Lowering Therapy ◽  
Glucose Lowering Therapy

<p><i>Objective</i>: Postpancreatitis diabetes mellitus (PPDM) is a type of secondary diabetes that requires special considerations for management. The main objective was to examine prescription patterns of glucose-lowering therapy among adults with PPDM compared to type 1 and type 2 diabetes.</p> <p><i>Research Design and Methods:</i> In a Danish nation-wide population-based cohort study we identified all individuals with adult-onset diabetes mellitus in the period 2000-2018 and categorized them as type 1 diabetes, type 2 diabetes or PPDM. We ascertained diabetes incidence rates, clinical and demographic characteristics, classifications and prescription patterns of glucose-lowering therapy and compared these parameters across diabetes subgroups. </p> <p><i>Results</i><i>:</i> Among 398,456 adults with new-onset diabetes mellitus, 5,879 (1.5%) had PPDM, 9,252 (2.3%) type 1 diabetes and the remaining type 2 diabetes (96.2%). The incidence rate of PPDM was 7.9 (95% CI 7.7-8.1) per 100,000 person-years vs. 12.5 (95% CI 12.2-12.7) for type 1 diabetes (incidence-rate-ratio 0.6; 95% CI 0.6-0.7, p<0.001). A sizeable proportion of PPDM patients were classified as type 2 diabetes (44.9%) and were prescribed sulfonylureas (25.2%) and incretin-based therapies (18.0%) that can potentially be harmful in PPDM. In contrast, 35.0% of patients never received biguanides, which are associated with a survival benefit in PPDM. Increased insulin requirements were observed for patients with PPDM compared to type 2 diabetes (hazard ratio 3.10; 95% CI 2.96-3.23, p<0.001) in particular for PPDM associated with chronic pancreatitis (hazard ratio 4.30; 95% CI 4.01-4.56, p<0.001).</p> <p><i>Conclusions</i><i>:</i> PPDM is a common type of secondary diabetes in adults but is often misclassified and treated as type 2 diabetes, although PPDM requires special considerations for management.</p>

An Approach to diabetic ketoacidosis in an emergency setting.

2020 ◽  
Vol 15 ◽  
Author(s):  
Dario Pitocco ◽  
Mauro Di Leo ◽  
Linda Tartaglione ◽  
Emanuele Gaetano Rizzo ◽  
Salvatore Caputo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Blood Glucose ◽  
Diabetic Ketoacidosis ◽  
Blood Glucose Concentration ◽  
Diabetic Complication ◽  
Emergency Setting ◽  
Online Activity

Background: Diabetic Ketoacidosis (DKA) is one of the most commonly encountered diabetic complication emergencies. It typically affects people with type 1 diabetes at the onset of the disease. It can also affect people with type 2 diabetes, although this is uncommon. Methods: Research and online content related to diabetes online activity is reviewed. DKA is caused by a relative or absolute deficiency of insulin and elevated levels of counter regulatory hormones. Results: Goals of therapy are to correct dehydration, acidosis and to reverse ketosis, gradually restoring blood glucose concentration to near normal. Conclusion: Furthermore it is essential to monitor potential complications of DKA and if necessary, to treat them and any precipitating events.

scholarly journals Differential Activation of CD8+Tumor-Specific Tc1 and Tc2 Cells by an IL-10-Producing Murine Plasmacytoma

1998 ◽  
Vol 6 (3-4) ◽  
pp. 331-342 ◽  
Author(s):  
Christoph Specht ◽  
Hans-Gerd Pauels ◽  
Christian Becker ◽  
Eckehart Kölsch
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Tumor Cells ◽  
T Cell Subsets ◽  
Early Stages ◽  
Specific Tolerance

The involvement of counteractiveCD8+T-cell subsets during tumor-specific immune responses was analyzed in a syngeneic murine plasmacytoma model.CD8+Tc cells against the immunogenic IL-10-producing BALB/c plasmacytoma ADJ-PC-5 can be easily induced by immunization of BALB/c mice with X-irradiated ADJ-PC-5 tumor cellsin vivoandin vitro. However, the failure of recipient mice to mount a protective Tc response against the tumor during early stages of a real or simulated tumor growth is not due to immunological ignorance, but depends on the induction of tumor-specific tolerance, involving a population of tumorinducedCD8+T cells that are able to inhibit the generation of tumor-specific Tc cells in a primary ADJ-PC-5-specific MLTC, using IFN-γas a suppressive factor. Whereas most longterm cultivated CD8+ADJ-PC-5-specific Tc lines produce type-1 cytokines on stimulation, at least two of them, which were derived from a primary MLTC, display a type-2 cytokine spectrum. Furthermore, the primaryin vitroTc response against ADJ-PC-5 cells shows characteristics of a Tc2 response. The Tc response is strictly depending on tumor-derived IL-10.CD8+Tc cells that are induced in a primary MLTC do not produce IFN-γ, and the tumor-specific Tc response is enhanced by IL-4 but suppressed by IFN-γor IL-12. In contrast, ADJ-PC- 5-specificCD8+Tc cells from immunized mice are IFN-γproducing Tc1 cells. Since the primaryin vitroTc response against the tumor is suppressed even by the smallest numbers of irradiated ADJ-PC-5-specific Tc1 cells via IFN-γthese Tc1 cells behave similar to the suppressiveCD8+T cells that are induced during early stages of ADJ-PC-5 tumorigenesis.

The Use of SGLT2i and GLP-1 RA in Patients with Type 2 Diabetes in Thailand: Evidence Review and Recommendations

2021 ◽  
Vol 104 (11) ◽  
pp. 1850-1865
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Lowering ◽  
Sodium Glucose Cotransporter ◽  
Evidence Review ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Lowering Therapy ◽  
The Cost ◽  
Selection Of

Background: Cardiovascular (CV) and renal comorbidities are common among type 2 diabetes (T2D) patients, and significantly increase the cost and burden of care. Both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve key outcomes including major CV events, hospitalization for heart failure, and renal outcomes, albeit to varying degrees in different T2D populations. Materials and Methods: The authors reviewed evidence from GLP-1 RA and SGLT2i CV outcomes trials and real-world studies in Thailand and elsewhere. Results: The authors formulated recommendations to guide selection of anti-diabetes medication based on patients’ clinical characteristics and CV or renal risk profile. Conclusion: These recommendations could help guide management of CV/renal comorbidities and risk alongside glucose-lowering therapy for individual patients. Keywords: Type 2 diabetes mellitus; Cardiovascular diseases; Chronic kidney disease; Clinical outcomes; SGLT2i; GLP-1 RA

scholarly journals Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice

2021 ◽  
Author(s):  
Miren Ettcheto ◽  
Elena Sánchez-Lopez ◽  
Amanda Cano ◽  
Marina Carrasco ◽  
Katherine Herrera ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Combined Therapy ◽  
Chronic Administration ◽  
Transgenic Animals ◽  
Amyloid Plaque ◽  
Tolerance Test ◽  
Metabolic Effects ◽  
Metabolic Disturbances ◽  
Insulin Tolerance

Abstract Background: Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20mg·kg-1·d-1) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD. Results: Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other pathways associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response.Conclusions: Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy.

scholarly journals A Nutraceutical Combination of Cinnamon, Purple Onion, and Tea Linked with Key Enzymes on Treatment of Type 2 Diabetes

2021 ◽  
Author(s):  
Lebin Weng ◽  
Ting-Hsu Chen ◽  
Liyue Huang ◽  
Dong Lai ◽  
Yaw-Syan Fu ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Maximal Response ◽  
Oral Glucose ◽  
Postprandial Plasma Glucose ◽  
Glucose Levels ◽  
High Fructose ◽  
Tea Extract

Abstract Background: Diabetes mellitus (DM) is concomitant with significant morbidity and mortality and its prevalence is accumulative worldwide. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; however, they may also cause adverse effects. This study explores the efficacy of polyherbal dietary supplement cinnamon, purple onion, and tea on the mediation of postprandial hyperglycemia for in the search of combinations with a maximal response. Materials and methods: A starch solution (3 g/kg Bwt) of oral starch tolerance test (OSTT) and glucose solution (4 g/kg Bwt) of oral glucose tolerance test (OGTT) with and without cinnamon, purple onion, tea extract (15 mg/kg Bwt), and mixture (each 5 mg/kg Bwt, 1:1:1), metformin (14 mg/kg Bwt), or acarbose (50 mg/kg Bwt) was administered to high fat plus high fructose-induced diabetic mice after an overnight fast. Postprandial plasma glucose levels were measured and incremental areas under the response curve were calculated. Results: Compared with acarbose, the mixture of extracts (purple onion, cinnamon, and tea) indicated decreasing blood glucose in OSTT. In OGTT, the mixture of extracts showed greater efficacy for hypoglycemia when compared with metformin. The molecular docking of α-Amylase, α-Glucosidase, and AMPK confirmed the putatively acting molecules from the extracts of purple onion, cinnamon, and tea. Conclusions: Overall, this investigation evidenced a beneficial mediation for the progression of lowering blood glucose with a combinatory extract of cinnamon, dietary onion, and tea, implicating their prospective as nutraceuticals that might ameliorate hyperglycemia in diabetes.

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