scholarly journals Leptin Improves Insulin Resistance and Hyperglycemia in a Mouse Model of Type 2 Diabetes

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 4024-4035 ◽  
Author(s):  
Yuka Toyoshima ◽  
Oksana Gavrilova ◽  
Shoshana Yakar ◽  
William Jou ◽  
Stephanie Pack ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Insulin Receptors ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Primary Defect ◽  
Peripheral Tissues ◽  
Liver And Pancreas ◽  
Insulin Responsiveness

Abstract Leptin has metabolic effects on peripheral tissues including muscle, liver, and pancreas, and it has been successfully used to treat lipodystrophic diabetes, a leptin-deficient state. To study whether leptin therapy can be used for treatment of more common cases of type 2 diabetes, we used a mouse model of type 2 diabetes (MKR mice) that show normal leptin levels and are diabetic due to a primary defect in both IGF-I and insulin receptors signaling in skeletal muscle. Here we show that leptin administration to the MKR mice resulted in improvement of diabetes, an effect that was independent of the reduced food intake. The main effect of leptin therapy was enhanced hepatic insulin responsiveness possibly through decreasing gluconeogenesis. In addition, the reduction of lipid stores in liver and muscle induced by enhancing fatty acid oxidation and inhibiting lipogenesis led to an improvement of the lipotoxic condition. Our data suggest that leptin could be a potent antidiabetic drug in cases of type 2 diabetes that are not leptin resistant.

scholarly journals Insulin and Insulin Receptors in Adipose Tissue Development

2019 ◽  
Vol 20 (3) ◽  
pp. 759 ◽  
Author(s):  
Angelo Cignarelli ◽  
Valentina Genchi ◽  
Sebastio Perrini ◽  
Annalisa Natalicchio ◽  
Luigi Laviola ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Insulin Receptor ◽  
Intracellular Signaling ◽  
Insulin Receptors ◽  
Metabolic Effects ◽  
Endocrine Activity ◽  
Differentiated Cells ◽  
And Function

Insulin is a major endocrine hormone also involved in the regulation of energy and lipid metabolism via the activation of an intracellular signaling cascade involving the insulin receptor (INSR), insulin receptor substrate (IRS) proteins, phosphoinositol 3-kinase (PI3K) and protein kinase B (AKT). Specifically, insulin regulates several aspects of the development and function of adipose tissue and stimulates the differentiation program of adipose cells. Insulin can activate its responses in adipose tissue through two INSR splicing variants: INSR-A, which is predominantly expressed in mesenchymal and less-differentiated cells and mainly linked to cell proliferation, and INSR-B, which is more expressed in terminally differentiated cells and coupled to metabolic effects. Recent findings have revealed that different distributions of INSR and an altered INSR-A:INSR-B ratio may contribute to metabolic abnormalities during the onset of insulin resistance and the progression to type 2 diabetes. In this review, we discuss the role of insulin and the INSR in the development and endocrine activity of adipose tissue and the pharmacological implications for the management of obesity and type 2 diabetes.

IL-6 signalling in exercise and disease

2007 ◽  
Vol 35 (5) ◽  
pp. 1295-1297 ◽  
Author(s):  
B.K. Pedersen
Keyword(s):  
Type 2 Diabetes ◽  
Dominant Negative ◽  
Metabolic Effects ◽  
Glucose Disposal ◽  
Acid Oxidation ◽  
Low Grade ◽  
Healthy Humans ◽  
Multinucleated Cells ◽  
Anti Inflammatory

Low-grade chronic inflammation is a feature of Type 2 diabetes and appears to play a pathogenetic role in insulin resistance. It is well known that cytokines, besides their immunoregulatory roles, are important players in metabolism. Moreover, it has become evident that skeletal muscles express several cytokines, which belong to distinct cytokine classes. IL-6 (interleukin-6) is a pleiotropic cytokine produced by virtually all multinucleated cells including skeletal myocytes where it is produced in response to contraction. IL-6 is subsequently released into the circulation, where it works in a hormone-like fashion to induce lipolysis and fat oxidation. In more recent experiments, it has been shown that IL-6 infusion increases glucose disposal during a hyperinsulinaemic euglycaemic clamp in healthy humans. IL-6 treatment of myotubes increases fatty acid oxidation, basal and insulin-stimulated glucose uptake and translocation of GLUT4 to the plasma membrane. Furthermore, IL-6 rapidly and markedly increases AMPK (AMP-activated protein kinase) and the metabolic effects of IL-6 were abrogated in AMPK dominant negative-infected cells. Finally, IL-6 mediates anti-inflammatory effects by stimulating the production of anti-inflammatory cytokines and by suppressing TNFα (tumour necrosis factor α) production. We suggest that IL-6 and other muscle-derived cytokines (myokines) may play a role in defending Type 2 diabetes.

scholarly journals Type 2 Diabetes Mellitus and Cancer: The Role of Pharmacotherapy

2016 ◽  
Vol 34 (35) ◽  
pp. 4261-4269 ◽  
Author(s):  
Gadi Shlomai ◽  
Brian Neel ◽  
Derek LeRoith ◽  
Emily Jane Gallagher
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Homeostasis ◽  
Cancer Incidence ◽  
Metabolic Effects ◽  
Peripheral Tissues ◽  
Cancer Data ◽  
Incidence And Mortality

Purpose Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent worldwide. Epidemiologic data suggest that T2DM is associated with an increased incidence and mortality from many cancers. The purpose of this review is to discuss the links between diabetes and cancer, the effects of various antidiabetic medications on cancer incidence and mortality, and the effects of anticancer therapies on diabetes. Design This study is a review of preclinical and clinical data regarding the effects of antidiabetic medications on cancer incidence and mortality and the effects of anticancer therapies on glucose homeostasis. Results T2DM is associated with an increased risk and greater mortality from many cancer types. Metformin use has been associated with a decrease in cancer incidence and mortality, and there are many ongoing randomized trials investigating the effects of metformin on cancer-related outcomes. However, data regarding the association of other antidiabetes medications with cancer incidence and mortality are conflicting. Glucocorticoids, hormone-based therapies, inhibitors that target the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin pathway, and insulin-like growth factor 1 receptor–targeted therapy have been associated with high rates of hyperglycemia. These agents mediate their deleterious metabolic effects by reducing insulin secretion and increasing insulin resistance in peripheral tissues. Conclusion Studies must be performed to optimize cancer screening strategies in individuals with T2DM. A greater understanding of the mechanisms that link diabetes and cancer are needed to identify targets for therapy in individuals with diabetes who develop cancer. Data from clinical studies are needed to further elucidate the effects of antidiabetic medications on cancer incidence and progression. As several anticancer therapies alter glucose homeostasis, physicians need to be aware of these potential effects. Careful patient screening and monitoring during treatment with these agents is necessary.

Structural analysis of tooth and jawbone in a type 2 diabetes mouse model

2014 ◽  
Author(s):  
Silvia Pabisch ◽  
Tsuguno Yamaguchi ◽  
Yasushi Koike ◽  
Kenji Egashira ◽  
Shinsuke Kataoka ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Structural Analysis ◽  
Mouse Model ◽  
Diabetes Mouse

Pharmacological Neprilysin Inhibition Improves Glucose Homeostasis in a Mouse Model of Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1825-P ◽  
Author(s):  
JACQUELINE H. PARILLA ◽  
STEVE MONGOVIN ◽  
BREANNE BARROW ◽  
NATHALIE ESSER ◽  
SAKENEH ZRAIKA
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Glucose Homeostasis ◽  
Neprilysin Inhibition

1734-P: High Dietary Fat Intake Exacerbates Insulin Resistance in a Type 2 Diabetes Genetic Mouse Model

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1734-P
Author(s):  
AUSTIN REILLY ◽  
SHIJUN YAN ◽  
ALEXA J. LONCHARICH ◽  
HONGXIA REN
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mouse Model ◽  
Dietary Fat ◽  
Fat Intake ◽  
Dietary Fat Intake ◽  
Genetic Mouse Model

Metformin: Up to Date

2020 ◽  
Vol 20 (2) ◽  
pp. 172-181 ◽  
Author(s):  
Silvia Sciannimanico ◽  
Franco Grimaldi ◽  
Fabio Vescini ◽  
Giovanni De Pergola ◽  
Massimo Iacoviello ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Current Literature ◽  
Weight Control ◽  
Low Cost ◽  
Hepatic Glucose Production ◽  
Metabolic Effects ◽  
Hypoglycemic Agents ◽  
Positive Effects ◽  
Mesh Terms

Background: Metformin is an oral hypoglycemic agent extensively used as first-line therapy for type 2 diabetes. It improves hyperglycemia by suppressing hepatic glucose production and increasing glucose uptake in muscles. Metformin improves insulin sensitivity and shows a beneficial effect on weight control. Besides its metabolic positive effects, Metformin has direct effects on inflammation and can have immunomodulatory and antineoplastic properties. Aim: The aim of this narrative review was to summarize the up-to-date evidence from the current literature about the metabolic and non-metabolic effects of Metformin. Methods: We reviewed the current literature dealing with different effects and properties of Metformin and current recommendations about the use of this drug. We identified keywords and MeSH terms in Pubmed and the terms Metformin and type 2 diabetes, type 1 diabetes, pregnancy, heart failure, PCOS, etc, were searched, selecting only significant original articles and review in English, in particular of the last five years. Conclusion: Even if many new effective hypoglycemic agents have been launched in the market in the last few years, Metformin would always keep a place in the treatment of type 2 diabetes and its comorbidities because of its multiple positive effects and low cost.

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