scholarly journals Potent PDE4 inhibitor activates AMPK and Sirt1 to induce mitochondrial biogenesis

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253269
Author(s):  
Sung-Jun Park ◽  
Faiyaz Ahmad ◽  
Robert J. Bahde ◽  
Andrew Philp ◽  
Jeonghan Kim ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Serum Glucose ◽  
Pde4 Inhibitor ◽  
Glucose Levels ◽  
Phosphodiesterase 4 ◽  
Energy Sensor ◽  
Evolutionarily Conserved ◽  
Sensor Activation ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is an evolutionarily conserved energy sensor. Activation of AMPK leads to a number of metabolic benefits, including improved mitochondrial function in skeletal muscle and lowering of serum glucose levels in type-2 diabetes models. However, direct activation of AMPK leads to cardiac enlargement, and an alternative strategy that activates AMPK without affecting the heart is needed. Inhibition of phosphodiesterase 4 (PDE4), which is poorly expressed in the human heart, activates AMPK in other tissues. In a screen to identify novel PDE4 inhibitors, we discovered compound CBU91, which is 5–10 fold more potent than rolipram, the best characterized PDE4 inhibitor. CBU91, like rolipram, is able to activate AMPK and Sirt1 and increase mitochondrial function in myotubes. These findings suggest that activation of AMPK in myotubes is a general property of PDE4 inhibition and that PDE4 inhibition may activate AMPK in metabolically relevant tissues without affecting the heart.

scholarly journals Effect of metformin on the expression of SNAER proteins in the skeletal muscle of rats with type 2 diabetes

2021 ◽  
pp. 270-278
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Serum Insulin ◽  
Serum Glucose ◽  
Snare Complex ◽  
Snare Proteins ◽  
Glucose Levels ◽  
Male Wistar Rats

Background and Aims: SNARE proteins are composed of a combination of SNAP-23, Stx-4, and VAMP-2 isoforms that are significantly expressed in skeletal muscle. These proteins control the transport of GLUT4 to the cell membranes. The modifications in the expression of SNARE proteins can cause Type 2 diabetes. The present study aimed to assess the effect of metformin on the expression of these proteins in rats. Materials and Methods: For the purpose of the study, 40 male Wistar rats were randomly selected. Streptozotocin and Nicotinamide were used for the induction of type 2 diabetes. The animals were assigned to five groups (n=8), including healthy and diabetic groups as control, as well as three experimental groups which were treated with different doses of metformin (100, 150, and 200 mg/kg body weight) for 30 days. The quantitative reverse transcription PCR (RT-qPCR) method was applied to evaluate the expression of SNARE complex proteins.. Results: Based on the results, metformin (100, 150, and 200 mg/kg body weight) decreased serum glucose levels and increased serum insulin levels. This difference in dose of 200 mg/kg body weight was statistically significant (P<0.05). Moreover, all three doses of metformin increased the expression of SNAP- 23, syntaxin-4, and VAMP-2 proteins in skeletal muscle tissue. Metformin at a dose of 200 mg/kg body weight demonstrated the most significant effects (P<0.05). Conclusion: As evidenced by the results of the current study, another anti-diabetic mechanism of metformin is to increase the expression of SNARE proteins, which effectively improves insulin resistance and lowers blood glucose.

scholarly journals VRK-1 extends life span by activation of AMPK via phosphorylation

2020 ◽  
Vol 6 (27) ◽  
pp. eaaw7824
Author(s):  
Sangsoon Park ◽  
Murat Artan ◽  
Seung Hyun Han ◽  
Hae-Eun H. Park ◽  
Yoonji Jung ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Life Span ◽  
Adult Life ◽  
Adult Life Span ◽  
C Elegans ◽  
Energy Sensor ◽  
Evolutionarily Conserved ◽  
Cultured Human Cells ◽  
Germline Proliferation ◽  
Amp Activated Protein Kinase

Vaccinia virus–related kinase (VRK) is an evolutionarily conserved nuclear protein kinase. VRK-1, the single Caenorhabditis elegans VRK ortholog, functions in cell division and germline proliferation. However, the role of VRK-1 in postmitotic cells and adult life span remains unknown. Here, we show that VRK-1 increases organismal longevity by activating the cellular energy sensor, AMP-activated protein kinase (AMPK), via direct phosphorylation. We found that overexpression of vrk-1 in the soma of adult C. elegans increased life span and, conversely, inhibition of vrk-1 decreased life span. In addition, vrk-1 was required for longevity conferred by mutations that inhibit C. elegans mitochondrial respiration, which requires AMPK. VRK-1 directly phosphorylated and up-regulated AMPK in both C. elegans and cultured human cells. Thus, our data show that the somatic nuclear kinase, VRK-1, promotes longevity through AMPK activation, and this function appears to be conserved between C. elegans and humans.

Sertraline-Induced Hyperglycemia: Case Report

2003 ◽  
Vol 33 (1) ◽  
pp. 103-105 ◽  
Author(s):  
Randy A. Sansone ◽  
Lori A. Sansone
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Empirical Studies ◽  
Serum Glucose ◽  
Increase Insulin Sensitivity ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Serotonergic Activity ◽  
Increase Insulin Secretion ◽  
Ssri Treatment

Empirical studies with humans suggest that selective serotonin reuptake inhibitors (SSRIs) may, through increases in serotonergic activity [1], increase insulin secretion [2], increase insulin sensitivity [3], and lower serum glucose levels [1]. Indeed, the potentially beneficial effects of SSRI treatment in diabetics are documented. However, we describe the case of a female, with diet-controlled, type 2 diabetes, whose glucose levels increased with exposure to sertraline.

scholarly journals Urate-lowering effects of dipeptidyl peptidase-4 inhibitors

2020 ◽  
Vol 23 (4) ◽  
pp. 349-356
Author(s):  
Taras S. Panevin ◽  
Olga V. Zhelyabina ◽  
Maxim S. Eliseev ◽  
Marina V. Shestakova
Keyword(s):  
Extracellular Fluid ◽  
Dipeptidyl Peptidase ◽  
Serum Glucose ◽  
Dipeptidyl Peptidase 4 ◽  
Glucose Levels ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Treatment Of Diabetes ◽  
Positive Effect ◽  
Metabolic Syndrome Components

Hyperuricemia is an increase of uric acid (UA) concentration in blood serum >420 pmol/L in men or >360 pmol/L in women and is considered to be a common biochemical abnormality. This condition shows that the extracellular fluid is oversaturated with urates, which concentration exceeds the limit of their solubility. This fact predisposes to the formation of crystals of sodium salt of UA and results in gout, urolithiasis, and other diseases. The frequent combination and relationship between purine and carbohydrate metabolism were noted in previous studies. In this regard, the choice of drugs for correcting these disorders should consider the possibility of a combined positive effect on the UA and serum glucose levels. The hypoglycemic drugs with pleiotropic effects on several metabolic syndrome components are considered to be of particular interest. Currently, one of the most frequently prescribed groups of drugs in the treatment of diabetes mellitus type 2 are dipeptidyl peptidase-4 inhibitors, which affect the level of incretins (gliptins). These drugs can be potentially attractive in patients with purine metabolism disorders since the available data indicate that these drugs affect UA level.

scholarly journals Sodium-glucose cotransporter-2-induced euglycemic diabetic ketoacidosis unmasks latent autoimmune diabetes in a patient misdiagnosed with type 2 diabetes mellitus: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Brian Vadasz ◽  
Mattan Arazi ◽  
Yousef Shukha ◽  
Ofir Koren ◽  
Riad Taher
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Ketoacidosis ◽  
Autoimmune Diabetes ◽  
Serum Glucose ◽  
Glucose Levels ◽  
Latent Autoimmune Diabetes ◽  
Sodium Glucose Cotransporter ◽  
Life Threatening ◽  
Euglycemic Diabetic Ketoacidosis

Abstract Background Euglycemic diabetic ketoacidosis is an uncommon but life-threatening complication associated with the use of sodium-glucose cotransporter 2 inhibitors that causes lower than expected blood glucose levels typically seen in diabetic ketoacidosis. Case presentation We present a case of 64-year-old Caucasian male patient previously diagnosed with type 2 diabetes treated with a sodium-glucose cotransporter 2 inhibitor who developed severe ketoacidosis. Serum glucose levels on initial presentation were slightly above normal baseline level. The patient was revealed to have latent autoimmune diabetes in adults. Conclusion This case highlights the importance of prescribing sodium-glucose cotransporter 2 inhibitors to the correct patient population and the significance of accurately differentiating between various types of diabetes.

scholarly journals A non-invasive method to estimate glucose levels in salivary secretions of diabetic patients

2019 ◽  
Vol 8 (1) ◽  
pp. 60
Author(s):  
Pramod Kumar Reddy Peddi ◽  
Chandra Babu Singanamala ◽  
Cheemalavagupalli Mounija
Keyword(s):  
Blood Glucose ◽  
Serum Glucose ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Glucose Levels ◽  
Oral Rinse ◽  
Non Invasive ◽  
Blood Glucose Levels ◽  
Type 2 Diabetic

Background: Aim of the study is to correlate between blood glucose levels and salivary glucose levels in type 2 diabetic patients, to study the relationship between salivary glucose levels and serum glucose levels in type 2 diabetic patients and to determine whether salivary glucose levels could be used as a non-invasive tool for the measurement of glycemic control in type 2 diabetics. This requirement of multiple pricking at regular intervals for monitoring serum glucose levels in the body is physically and psychologically traumatic to the patient. This necessitates a non-invasive procedure like salivary glucose estimation.Methods: The study population consisted of two groups: Group 1 consisted of 20 controlled diabetics and Group 2 consisted of 20 diabetics based on their random blood and salivary glucose levels. Two milliliters of peripheral blood were collected for the estimation of random blood glucose levels. Unstimulated saliva was collected by the oral rinse technique for the estimation of salivary glucose.Results: ANOVA single factor and Pearson correlation coefficient was carried out to know the statistical significance between the two groups. The salivary glucose levels were significantly higher in controlled and when compared with the diabetics. The salivary glucose levels showed a significant correlation with blood glucose levels, suggesting that salivary glucose levels can be used as a monitoring tool for predicting glycemic in diabetic patients.Conclusions: The present study found that estimation of salivary glucose levels can be used as a non-invasive, painless technique for the measurement of diabetic status of a patient in a dental set up.

scholarly journals A mio-inozitol jótékony hatása inzulint igénylő 2-es típusú cukorbetegséghez társuló polycystás ovarium szindrómás várandós terápiájában

2017 ◽  
Vol 158 (14) ◽  
pp. 541-545
Author(s):  
Attila Kun ◽  
János Tornóczky
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Polycystic Ovary ◽  
Folic Acid Supplementation ◽  
Serum Glucose ◽  
Glucose Levels ◽  
Developmental Disturbances ◽  
Gestational Week

Abstract: Authors would like to demonstrate the beneficial effect of myo-inositol supplementation in a pregnant woman with insulin-dependent type 2 diabetes mellitus and polycystic ovary syndrome. Insulin and metformin treatment could not achieve normalization of glucose homeostasis for 3 years, and hypoglycemic episodes were frequent. Myo-inositol and folic acid supplementation added to the basic treatment resulted in improved glucose levels in 2 months. At this time she became pregnant. During pregnancy serum glucose levels still improved in the next 2 months. The amniotic membrane ruptured at the 19th gestational week, and pregnancy had to be finished. Developmental disturbances were excluded by the pathologist. She became pregnant again and gave birth to a premature male neonate at the 29th gestational week. The aim of the report was to demonstrate that myo-inositol supplementation may improve the efficacy of the therapy in type 2 diabetes mellitus. Orv. Hetil., 2017, 158(14), 541–545.

scholarly journals Poor Metabolic Health Increases COVID-19-Related Mortality in the UK Biobank Sample

2021 ◽  
Vol 12 ◽  
Author(s):  
Filip Morys ◽  
Alain Dagher
Keyword(s):  
Waist Circumference ◽  
Serum Glucose ◽  
Metabolic Health ◽  
Uk Biobank ◽  
Glucose Levels ◽  
Increased Risk ◽  
Confounding Variables ◽  
Specific Factors ◽  
The Uk

Previous studies link obesity and components of metabolic health, such as hypertension or inflammation, to increased hospitalizations and mortality of patients with COVID-19. Here, in two overlapping samples of over 1,000 individuals from the UK Biobank we investigate whether metabolic health as measured by waist circumference, dyslipidemia, hypertension, type 2 diabetes, and systemic inflammation is related to increased COVID-19 infection and mortality rate. Using logistic regression and controlling for confounding variables such as socioeconomic status, age, sex or ethnicity, we find that individuals with worse metabolic health (measured on average eleven years prior to 2020) have an increased risk for COVID-19-related death (adjusted odds ratio: 1.75). We also find that specific factors contributing to increased mortality are increased serum glucose levels, systolic blood pressure and waist circumference.

scholarly journals Diagnosis and treatment of pediatric type 2 diabetes mellitus

2021 ◽  
Vol 64 (6) ◽  
pp. 432-437
Author(s):  
Hae Sang Lee
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Children And Adolescents ◽  
Pancreatic Beta Cell ◽  
Serum Glucose ◽  
Diagnosis And Treatment ◽  
Glucose Levels ◽  
Glucagon Like Peptide 1

Background: Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases, and its increasing prevalence in children and adolescents is a worldwide problem. In the past ten years, the prevalence of T2DM has increased by more than two-fold. This review focuses on the recent advances in the diagnosis and treatment of T2DM in children and adolescents.Current Concepts: Pancreatic beta-cell dysfunction and insulin resistance are the key factors contributing to the development of T2DM. The diagnosis of T2DM is based on serum glucose levels or hemoglobin A1c levels. Currently, only insulin, metformin, and liraglutide (glucagon-like peptide-1 receptor agonist) have been approved for the treatment of T2DM in children and adolescents.Discussion and Conclusion: Early diagnosis and prevention of T2DM in children and adolescents are essential. Furthermore, the treatment of T2DM in children and adolescents is limited, unlike in adults. Further research is needed to evaluate the long-term efficacy and safety of the available treatments in children and adolescents with T2DM.

scholarly journals Types of Dyslipidemia in Type 2 DM Patients of Bhubaneswar region

2015 ◽  
Vol 1 (1) ◽  
pp. 33-36
Author(s):  
Rajendra Dev Bhatt ◽  
Kamal Lochan
Keyword(s):  
Lipid Profile ◽  
Tertiary Hospital ◽  
Diabetic Control ◽  
Serum Glucose ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Control Subjects ◽  
Preventable Risk Factor ◽  
And Control

BACKGROUND: A characteristic pattern, termed dyslipidemia, consists of deranged of any single components of lipid profile test. This pattern is most frequently seen in diabetes and may be a preventable risk factor for subsequent cardiovascular disease. This study determined the influence of type 2 diabetes mellitus (T2DM) on lipid profile of diabetic patients reporting in a tertiary hospital in Bhubaneswar, India. METHODS: 50 confirmed T2DM patients and 50 non-diabetic control subjects were selected for the study. Fasting and 2 hours post prandial blood samples were collected from both study and control patients. Fasting blood sample was analyzed for lipid profile test and serum glucose, and post prandial sample was analyzed for serum glucose only. RESULTS: Sixty two (62%) of diabetic patients were males whilst thirty eight (38%) were females in this study. The mean plasma glucose levels, Total cholesterol and Triacylglycerol were significantly raised in the diabetics as compared to those in the control subjects. This is substantiated by the fact that the entire lipid fractions are disturbed in diabetics as compared to healthy controls. CONCLUSION: Thus dyslipidemia was quite common in diabetes and Hypertriglyceridemia was the most common one. DOI: http://dx.doi.org/10.3126/acclm.v1i1.12313 Ann. Clin. Chem. & Lab. Med. 1(1) 2015: 33-36

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