scholarly journals Role of Melanocortin Signaling in Neuroendocrine and Metabolic Actions of Leptin in Male Rats With Uncontrolled Diabetes

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4157-4167 ◽  
Author(s):  
Thomas H. Meek ◽  
Miles E. Matsen ◽  
Vincent Damian ◽  
Alex Cubelo ◽  
Streamson C. Chua ◽  
...  
Keyword(s):  
Male Rats ◽  
Melanocortin Receptor ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Uncontrolled Diabetes ◽  
Streptozotocin Induced Diabetes ◽  
Melanocortin Signaling ◽  
Antidiabetic Effects

Abstract Although the antidiabetic effects of leptin require intact neuronal melanocortin signaling in rodents with uncontrolled diabetes (uDM), increased melanocortin signaling is not sufficient to mimic leptin's glucose-lowering effects. The current studies were undertaken to clarify the role of melanocortin signaling in leptin's ability to correct metabolic and neuroendocrine disturbances associated with uDM. To accomplish this, bilateral cannulae were implanted in the lateral ventricle of rats with streptozotocin-induced diabetes, and leptin was coinfused with varying doses of the melanocortin 3/4 receptor (MC3/4R) antagonist, SHU9119. An additional cohort of streptozotocin-induced diabetes rats received intracerebroventricular administration of either the MC3/4R agonist, melanotan-II, or its vehicle. Consistent with previous findings, leptin's glucose-lowering effects were blocked by intracerebroventricular SHU9119. In contrast, leptin-mediated suppression of hyperglucagonemia involves both melanocortin dependent and independent mechanisms, and the degree of glucagon inhibition was associated with reduced plasma ketone body levels. Increased central nervous system melanocortin signaling alone fails to mimic leptin's ability to correct any of the metabolic or neuroendocrine disturbances associated with uDM. Moreover, the inability of increased melanocortin signaling to lower diabetic hyperglycemia does not appear to be secondary to release of the endogenous MC3/4R inverse agonist, Agouti-related peptide (AgRP), because AgRP knockout mice did not show increased susceptibility to the antidiabetic effects of increased MC3/4R signaling. Overall, these data suggest that 1) AgRP is not a major driver of diabetic hyperglycemia, 2) mechanisms independent of melanocortin signaling contribute to leptin's antidiabetic effects, and 3) melanocortin receptor blockade dissociates leptin's glucose-lowering effect from its action on other features of uDM, including reversal of hyperglucagonemia and ketosis, suggesting that brain control of ketosis, but not blood glucose levels, is glucagon dependent.

scholarly journals Role of POMC and AgRP neuronal activities on glycaemia in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aykut Göktürk Üner ◽  
Onur Keçik ◽  
Paula G. F. Quaresma ◽  
Thiago M. De Araujo ◽  
Hyon Lee ◽  
...  
Keyword(s):  
Neuronal Firing ◽  
Designer Drugs ◽  
Lower Blood Glucose ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Neuronal Populations ◽  
Blood Glucose Levels ◽  
Lower Blood ◽  
Stimulation Of

Abstract Leptin regulates both feeding and glycaemia primarily through its receptors expressed on agouti-related peptide (AgRP) and pro-opiomelanocortin-expressing (POMC) neurons; however, it is unknown whether activity of these neuronal populations mediates the regulation of these processes. To determine this, we injected Cre-dependent designer receptors exclusively activated by designer drugs (DREADD) viruses into the hypothalamus of normoglycaemic and diabetic AgRP-ires-cre and POMC-cre mice to chemogenetically activate or inhibit these neuronal populations. Despite robust changes in food intake, activation or inhibition of AgRP neurons did not affect glycaemia, while activation caused significant (P = 0.014) impairment in insulin sensitivity. Stimulation of AgRP neurons in diabetic mice reversed leptin’s ability to inhibit feeding but did not counter leptin’s ability to lower blood glucose levels. Notably, the inhibition of POMC neurons stimulated feeding while decreasing glucose levels in normoglycaemic mice. The findings suggest that leptin’s effects on feeding by AgRP neurons are mediated by changes in neuronal firing, while the control of glucose balance by these cells is independent of chemogenetic activation or inhibition. The firing-dependent glucose lowering mechanism within POMC neurons is a potential target for the development of novel anti-diabetic medicines.

scholarly journals SYNTHESIS OF CR(III)-ASPARTATE AND CU(II)-ASPARTATE COMPLEXES AS ANTIDIABETIC COMPOUND

2021 ◽  
pp. 539-547
Author(s):  
Sutopo Hadi ◽  
Yuli Ambarwati ◽  
Dinda S. Firguna ◽  
Syaiful Bahri ◽  
Aspita Laila
Keyword(s):  
Blood Glucose ◽  
Aspartic Acid ◽  
Analysis Of Variance ◽  
Mus Musculus ◽  
Antidiabetic Activity ◽  
Male Mice ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Antidiabetic Effects

The synthesis of Cr(III)-Aspartate and Cu(II)-Aspartate complexes has been successfully conducted by reacting CrCl3·6H2O and CuCl2·2H2O metals with aspartic acid. Therefore, this study aimed to synthesize Cr(Asp)2Cl2 and Cu(Asp)Cl2 as well as test their antidiabetic effects. The synthesis results of Cr(Asp)2Cl2 and Cu(Asp)Cl2 in the form of light purple and blue solids were 0.3001 g and 0.3095g with a yield of 95.14% and 95.02%, respectively. Furthermore, the antidiabetic test used 27 male mice (Mus musculus) with nine treatments for 21 days. The data obtained were analyzed statistically using analysis of variance, and the antidiabetic activity was expressed in percent glucose lowering. The result showed a decrease in blood glucose levels in mice after alloxan induction, with percent glucose lowering (%GL) values of 74.1874% for Cr(Asp)2Cl2 and 76.1337% for Cu(Asp)Cl2 compounds. Therefore, the Cr(Asp)2Cl2 and Cu(Asp)Cl2 compounds can be used as antidiabetic in mice which are also potentially used as metal-based drugs for the treatment of DM.

scholarly journals Role of Insulin in Health and Disease: An Update

2021 ◽  
Vol 22 (12) ◽  
pp. 6403
Author(s):  
Md Saidur Rahman ◽  
Khandkar Shaharina Hossain ◽  
Sharnali Das ◽  
Sushmita Kundu ◽  
Elikanah Olusayo Adegoke ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Basic Research ◽  
Future Research ◽  
Protective Effects ◽  
Glucose Levels ◽  
Physiological Processes ◽  
Blood Glucose Levels ◽  
Wide Range ◽  
Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

scholarly journals Effects of peptidic growth hormone secretagogue receptor (GHS-R) antagonist [D-Lys3] on some of serum hormonal and biochemical parameters in Wistar rat model

2014 ◽  
Vol 58 (3) ◽  
pp. 288-291 ◽  
Author(s):  
Habib Aghdam Shahryar ◽  
Alireza Lotfi
Keyword(s):  
Total Protein ◽  
Biochemical Parameters ◽  
Serum Lipids ◽  
Considerable Increase ◽  
Wistar Rat ◽  
Male Rats ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Glucose Levels ◽  
Blood Glucose Levels

Objective : The present study investigated the effects of different dosages of a GHS-R antagonist [D-Lys3] on some serum hormonal (cortisol, T3 and T4) and biochemical parameters in a rat.Materials and methods : Thirty-six 60-day-old male rats were assigned to four treatments. [D-Lys3]-GHRP-6 solutions were infused via intraperitoneal injections. Blood was collected and analyzed.Results : The large dosages of a GHS-R antagonist (200 ng/kg BW) caused increases in cortisol, whereas no significant changes occurred when low dosages were injected. There were no significant changes in T3 and T4 following the administration of the GHS-R antagonist, but a considerable increase was observed in blood glucose levels of the groups (G50, G100, and G200 ng/kg BW). There was a significant increase in total protein when the greatest dose was administrated (G200 ng/kg BW). However, total cholesterol, triglycerides, and albumin showed no significant changes.Conclusions : Exogenous GHS-R antagonist can cause an increase in glucose and moderate increases in cortisol and total protein, yet it has no significant effect on T3 and T4 levels or on the concentrations of serum lipids. The effect of GHS-R antagonist is not completely adverse to the effects of ghrelin. Further molecular studies are necessary to identify the physiological effects of the peptidic GHS-R antagonist. Arq Bras Endocrinol Metab. 2014;58(3):288-91

scholarly journals Platelet Effects of Anti-diabetic Therapies: New Perspectives in the Management of Patients with Diabetes and Cardiovascular Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Annunziata Nusca ◽  
Dario Tuccinardi ◽  
Silvia Pieralice ◽  
Sara Giannone ◽  
Myriam Carpenito ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Large Population ◽  
Optimal Management ◽  
Direct And Indirect Effects ◽  
Thrombotic Risk ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Patients With Diabetes

In type 2 diabetes, anti-thrombotic management is challenging, and current anti-platelet agents have demonstrated reduced efficacy. Old and new anti-diabetic drugs exhibited—besides lowering blood glucose levels—direct and indirect effects on platelet function and on thrombotic milieu, eventually conditioning cardiovascular outcomes. The present review summarizes existing evidence on the effects of glucose-lowering agents on platelet properties, addressing pre-clinical and clinical research, as well as drug–drug interactions with anti-platelet agents. We aimed at expanding clinicians’ understanding by highlighting new opportunities for an optimal management of patients with diabetes and cardiovascular disease. We suggest how an improvement of the thrombotic risk in this large population of patients may be achieved by a careful and tailored combination of anti-diabetic and anti-platelet therapies.

scholarly journals Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia

Endocrinology ◽  
2010 ◽  
Vol 152 (2) ◽  
pp. 394-404 ◽  
Author(s):  
Jonathan P. German ◽  
Joshua P. Thaler ◽  
Brent E. Wisse ◽  
Shinsuke Oh-I ◽  
David A. Sarruf ◽  
...  
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Underlying Mechanism ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Uncontrolled Diabetes ◽  
Urinary Glucose ◽  
Hepatic Glucose ◽  
Glucose Excretion ◽  
The Brain

Abstract The brain has emerged as a target for the insulin-sensitizing effects of several hormonal and nutrient-related signals. The current studies were undertaken to investigate mechanisms whereby leptin lowers circulating blood glucose levels independently of insulin. After extending previous evidence that leptin infusion directly into the lateral cerebral ventricle ameliorates hyperglycemia in rats with streptozotocin-induced uncontrolled diabetes mellitus, we showed that the underlying mechanism is independent of changes of food intake, urinary glucose excretion, or recovery of pancreatic β-cells. Instead, leptin action in the brain potently suppresses hepatic glucose production while increasing tissue glucose uptake despite persistent, severe insulin deficiency. This leptin action is distinct from its previously reported effect to increase insulin sensitivity in the liver and offers compelling evidence that the brain has the capacity to normalize diabetic hyperglycemia in the presence of sufficient amounts of central nervous system leptin.

Prediabetes, undiagnosed diabetes and diabetes risk in Italy in 2017–2018: results from the first National screening campaign in community pharmacies

2021 ◽  
Author(s):  
P Brunetti ◽  
L Baldessin ◽  
S Pagliacci
Keyword(s):  
High Risk ◽  
Diabetes Risk ◽  
World Health ◽  
Undiagnosed Diabetes ◽  
Community Pharmacies ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Health Organization ◽  
Very High

Abstract Background Effective policies for diabetes prevention remain urgent. We conducted a mass screening campaign in Italy to identify subjects potentially having undiagnosed diabetes, prediabetes or at diabetes risk. Methods This cohort study was conducted in community pharmacies joining the unitary National federation of pharmacy holders (Federfarma) and participating in the 7-day screening campaign ‘DiaDay’ in 2017–2018. Capillary blood glucose levels and the risk of developing diabetes in 10 years (through the Finnish Diabetes Risk Score) were assessed. Results 145 651 volunteers aged ≥20 years without known diabetes were screened at 5671 community pharmacies in 2017 and 116 097 at 5112 in 2018. Overall, 3.6% had glucose values suggestive of undiagnosed diabetes; under fasting conditions (N = 94 076), 39.9% and 16.4% had values suggestive of prediabetes by the American Diabetes Association and the World Health Organization criteria, respectively. Of those without diabetes (N = 252 440), 19.2% had scores compatible with a high risk (1:3) and 2.7% with a very high risk (1:2) of developing the disease; in the prediabetes group, the risk rose with higher impaired fasting glucose values. Conclusions DiaDay, the first National screening campaign, highlights the need to screen the population and the key role of the pharmacist both in screening activities and education promotion.

scholarly journals Gastrointestinal Mechanisms Underlying the Cardiovascular Effect of Metformin

2020 ◽  
Vol 13 (11) ◽  
pp. 410
Author(s):  
Malcolm J. Borg ◽  
Christopher K. Rayner ◽  
Karen L. Jones ◽  
Michael Horowitz ◽  
Cong Xie ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Cardiovascular Effect ◽  
Elevated Blood ◽  
Direct Effects ◽  
Mechanistic Studies ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Blood Glucose Levels

Metformin, the most widely prescribed drug therapy for type 2 diabetes, has pleiotropic benefits, in addition to its capacity to lower elevated blood glucose levels, including mitigation of cardiovascular risk. The mechanisms underlying the latter remain unclear. Mechanistic studies have, hitherto, focused on the direct effects of metformin on the heart and vasculature. It is now appreciated that effects in the gastrointestinal tract are important to glucose-lowering by metformin. Gastrointestinal actions of metformin also have major implications for cardiovascular function. This review summarizes the gastrointestinal mechanisms underlying the action of metformin and their potential relevance to cardiovascular benefits.

The Role of Biomaterials in Insulin Delivery Systems

1980 ◽  
Vol 3 (5) ◽  
pp. 299-304 ◽  
Author(s):  
S.D. Bruck
Keyword(s):  
Blood Glucose ◽  
Glucose Sensor ◽  
Insulin Delivery ◽  
The United States ◽  
Delivery Systems ◽  
Open Loop ◽  
Health Concern ◽  
Glucose Levels ◽  
Blood Glucose Levels

The control of blood glucose levels in diabetes involving devices are critically reviewed, and the role of blood-contacting biomaterial components analyzed. These include mechanical insulin-delivery systems of the closed-loop type that require an electronic glucose sensor and feedback, and open-loop systems that deliver insulin without a sensor and feedback. Whole pancreatic and islet transplantations, islet encapsulation, and the potential role of polymeric sustained drug delivery systems are discussed. The medical and social impacts of diabetes mellitus are of prime public health concern and of even greater magnitude than those of heart disease in the United States. While future advances in device design, miniaturization, and biometrials technology will significantly add to the arsenal of therapeutic alternatives, devices capable of controlling blood glucose levels ought to be viewed as mere interim phases rather than as final goals of the problem.

Liver glycogen content decreases during meals in rats

1982 ◽  
Vol 243 (3) ◽  
pp. R450-R453
Author(s):  
W. Langhans ◽  
N. Geary ◽  
E. Scharrer
Keyword(s):  
Blood Glucose ◽  
Glycogen Content ◽  
Liver Glycogen ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Liver Glycogen Content ◽  
Ad Libitum ◽  
Portal Veins ◽  
Hepatic Portal

The effects of feeding on liver glycogen content and blood glucose in the hepatic and hepatic portal veins were investigated in rats. Liver glycogen content decreased about 25% during meals both in rats refed after 12 h food deprivation (23 +/- 1 to 17 +/- 1 mg glycogen/g liver) and in ad libitum-fed rats taking fully spontaneous meals (44 +/- 2 to 32 +/- 2 mg/g). Liver glycogen began to increase within 30 min after meals in ad libitum-fed rats. Hepatic vein blood glucose levels at meal onset (118 +/- 4 mg/dl in the food-deprived rats, 127 +/- 4 in ad libitum-fed rats) and at meal end (155 +/- 3 and 166 +/- 5 mg/dl, respectively) were similar in the two groups. Portal vein blood glucose increased during meals in the previously food-deprived rats (83 +/- 4 to 116 +/- 6 mg/dl) but not in the ad libitum-fed rats (127 +/- 5 to 132 +/- 3 mg/dl). Mechanisms that may elicit prandial glycogenolysis and the possible role of this effect in the production of meal ending satiety are discussed.

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