Cyclin-Dependent Kinase 5/p35/p39: A Novel and Imminent Therapeutic Target for Diabetes Mellitus

Present therapies to minify hyperglycaemia and insulin resistance mainly target ATP-sensitive K+channels () of pancreatic cells and PPAR-γto enhance the insulin secretion and potential for GLUT expression, respectively. These current approaches are frequently associated with the various side effects such as hypoglycaemia and cardiovascular adverse events. CDK5 is a serine/threonine protein kinase, which forms active complexes with p35 or p39 found principally in neurons and in pancreaticβcells. Pieces of evidence from recent studies recommend the vital role of CDK5 in physiological functions in nonneuronal cells such as glucose-stimulated insulin secretion in pancreatic cells. Inhibition of CDK5 averts the decrease of insulin gene expression through the inhibition of nuclear translocation of PDX-1 which is a transcription factor for the insulin gene. The present pieces of evidence designate that CDK5 might be a potential drug target for the regulation of glucose-stimulated insulin secretion in the treatment of diabetes mellitus.

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Potential Of Sambung Nyawa Leaves (Gynura Procumbens) As An Antidiabetic Medicine

Eureka Herba Indonesia ◽

10.37275/ehi.v1i2.8 ◽

2020 ◽

Vol 1 (2) ◽

pp. 32-35

Author(s):

Mustofa

Keyword(s):

Diabetes Mellitus ◽

Metabolic Disease ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Blood Sugar ◽

Review Article ◽

Flavonoid Content ◽

Antidiabetic Therapy ◽

Treatment Of Diabetes

Diabetes mellitus is a metabolic disease characterized by an increase in blood sugardue to defects in insulin secretion, insulin sensitivity, or both. The number ofpeople with diabetes mellitus in Indonesia has increased every year. The numberof people with diabetes is 6.9% in 2013 to 10.9% in 2018. Various therapies have beencarried out for the treatment of Diabetes Mellitus, one of which is herbal therapy.Gynura Procumbens is a plant that is widely used as a treatment for diabetes mellitus,kidney, rash and fever, and hypertension. The flavonoid content in GynuraProcumben replaces the decrease in blood sugar. This review article attempts toexplain the role of Gynura Procumbens as an antidiabetic therapy in previous studies.The method used in this article is through searching articles through the NCBIdatabase and Google Scholar. The results of an article search found that GynuraProcumben has antidiabetic potential which can reduce blood sugar in patients withDiabetes Mellitus

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mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells

Journal of Endocrinology ◽

10.1530/joe-12-0351 ◽

2012 ◽

Vol 216 (1) ◽

pp. 21-29 ◽

Cited By ~ 21

Author(s):

Olivier Le Bacquer ◽

Gurvan Queniat ◽

Valery Gmyr ◽

Julie Kerr-Conte ◽

Bruno Lefebvre ◽

...

Keyword(s):

Insulin Secretion ◽

Cell Function ◽

Antagonistic Effect ◽

Dominant Negative ◽

Insulin Content ◽

Insulin Biosynthesis ◽

Direct Role ◽

Β Cell Function ◽

Glucose Stimulated Insulin Secretion

Regulated associated protein of mTOR (Raptor) and rapamycin-insensitive companion of mTOR (rictor) are two proteins that delineate two different mTOR complexes, mTORC1 and mTORC2 respectively. Recent studies demonstrated the role of rictor in the development and function of β-cells. mTORC1 has long been known to impact β-cell function and development. However, most of the studies evaluating its role used either drug treatment (i.e. rapamycin) or modification of expression of proteins known to modulate its activity, and the direct role of raptor in insulin secretion is unclear. In this study, using siRNA, we investigated the role of raptor and rictor in insulin secretion and production in INS-1 cells and the possible cross talk between their respective complexes, mTORC1 and mTORC2. Reduced expression of raptor is associated with increased glucose-stimulated insulin secretion and intracellular insulin content. Downregulation of rictor expression leads to impaired insulin secretion without affecting insulin content and is able to correct the increased insulin secretion mediated by raptor siRNA. Using dominant-negative or constitutively active forms of Akt, we demonstrate that the effect of both raptor and rictor is mediated through alteration of Akt signaling. Our finding shed new light on the mechanism of control of insulin secretion and production by the mTOR, and they provide evidence for antagonistic effect of raptor and rictor on insulin secretion in response to glucose by modulating the activity of Akt, whereas only raptor is able to control insulin biosynthesis.

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JTT-608 controls blood glucose by enhancement of glucose-stimulated insulin secretion in normal and diabetes mellitus rats

European Journal of Pharmacology ◽

10.1016/s0014-2999(98)00952-2 ◽

1999 ◽

Vol 367 (1) ◽

pp. 91-99 ◽

Cited By ~ 11

Author(s):

Takeshi Ohta ◽

Noboru Furukawa ◽

Fumihiko Yonemori ◽

Korekiyo Wakitani

Keyword(s):

Diabetes Mellitus ◽

Insulin Secretion ◽

Blood Glucose ◽

Glucose Stimulated Insulin Secretion

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The Role of Natural Products on Diabetes Mellitus Treatment: A Systematic Review of Randomized Controlled Trials

Pharmaceutics ◽

10.3390/pharmaceutics14010101 ◽

2022 ◽

Vol 14 (1) ◽

pp. 101

Author(s):

Lucía Vivó-Barrachina ◽

María José Rojas-Chacón ◽

Rocío Navarro-Salazar ◽

Victoria Belda-Sanchis ◽

Javier Pérez-Murillo ◽

...

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Natural Products ◽

Promising Therapeutic Target ◽

Prevalent Disease ◽

Bibliographic Search ◽

Treatment Of Diabetes ◽

Definition Of ◽

Diabetes Mellitus Treatment

The present study was carried out to relate the role of natural products in the metabolism of an increasingly prevalent disease, type 2 diabetes mellitus. At present, in addition to the pharmacological resources, an attempt is being made to treat diabetes mellitus with natural products. We carried out a systematic review of studies focusing on the role of natural products on diabetes mellitus treatment. The bibliographic search was done through Medline (Pubmed) and Web of Science. From 193 records, the title and summary of each were examined according to the criteria and whether they met the selection criteria. A total of 15 articles were included; after reviewing the literature, it is apparent that the concept of natural products is ambiguous as no clear boundary has been established between what is natural and what is synthetic, therefore we feel that a more explicit definition of the concept of “natural product” is needed. Gut microbiota is a promising therapeutic target in the treatment of diabetes. Therefore, it would be necessary to work on the relationship between the microbiome and the benefits in the treatment of diabetes mellitus. Treatment based solely on these natural products is not currently recommended as more studies are needed.

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Role of Metallic Nanoparticles in the Treatment of Diabetes Mellitus

Indo Global Journal of Pharmaceutical Sciences ◽

10.35652/igjps.2019.92s19 ◽

2019 ◽

Vol 09 (02) ◽

pp. 121-121

Author(s):

Yogita Kumari ◽

Gurmandeep Kaur ◽

Clarisse Ayinkamiye ◽

Sachin Kumar Singh ◽

Rajesh Kumar ◽

...

Keyword(s):

Diabetes Mellitus ◽

Metallic Nanoparticles ◽

Treatment Of Diabetes

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The Emerging Role of Thiazolidinediones in the Treatment of Diabetes-Mellitus and Related Disorders

Clinical and Experimental Hypertension ◽

10.3109/10641969909068655 ◽

1999 ◽

Vol 21 (1-2) ◽

pp. 121-136 ◽

Cited By ~ 8

Author(s):

S. Subramaniam

Keyword(s):

Diabetes Mellitus ◽

Treatment Of Diabetes

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miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus

Mediators of Inflammation ◽

10.1155/2019/4851214 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Pingping Wang ◽

Zengfang Wang ◽

Guojie Liu ◽

Chengwen Jin ◽

Quan Zhang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Macrophage Polarization ◽

Vital Role ◽

Luciferase Reporter ◽

M2 Macrophage ◽

And Migration

MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.

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Role of S20G mutation of amylin gene in insulin secretion, insulin sensitivity, and Type II diabetes mellitus in Taiwanese patients

Diabetologia ◽

10.1007/s001250051060 ◽

1998 ◽

Vol 41 (10) ◽

pp. 1250-1251 ◽

Cited By ~ 10

Author(s):

Not Available Not Available

Keyword(s):

Diabetes Mellitus ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Type Ii Diabetes ◽

Type Ii Diabetes Mellitus ◽

Type Ii ◽

S20g Mutation ◽

Amylin Gene

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Metabolic cycling in control of glucose-stimulated insulin secretion

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90604.2008 ◽

2008 ◽

Vol 295 (6) ◽

pp. E1287-E1297 ◽

Cited By ~ 157

Author(s):

Mette V. Jensen ◽

Jamie W. Joseph ◽

Sarah M. Ronnebaum ◽

Shawn C. Burgess ◽

A. Dean Sherry ◽

...

Keyword(s):

Insulin Secretion ◽

Β Cells ◽

Pyruvate Metabolism ◽

Coupling Factors ◽

Stimulus Secretion Coupling ◽

Channel Dependent ◽

Glucose Stimulated Insulin Secretion ◽

Dependent Mechanism

Glucose-stimulated insulin secretion (GSIS) is central to normal control of metabolic fuel homeostasis, and its impairment is a key element of β-cell failure in type 2 diabetes. Glucose exerts its effects on insulin secretion via its metabolism in β-cells to generate stimulus/secretion coupling factors, including a rise in the ATP/ADP ratio, which serves to suppress ATP-sensitive K+ (KATP) channels and activate voltage-gated Ca2+ channels, leading to stimulation of insulin granule exocytosis. Whereas this KATP channel-dependent mechanism of GSIS has been broadly accepted for more than 30 years, it has become increasingly apparent that it does not fully describe the effects of glucose on insulin secretion. More recent studies have demonstrated an important role for cyclic pathways of pyruvate metabolism in control of insulin secretion. Three cycles occur in islet β-cells: the pyruvate/malate, pyruvate/citrate, and pyruvate/isocitrate cycles. This review discusses recent work on the role of each of these pathways in control of insulin secretion and builds a case for the particular relevance of byproducts of the pyruvate/isocitrate cycle, NADPH and α-ketoglutarate, in control of GSIS.

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