Molecular Mechanism of Corticosteroid-Induced Hyperglycemia

Corticosteroids are widely used as strong anti-inflammatory and immunosuppressive drugs to treat various diseases. However, the use of corticosteroids can cause several side effects, such as hyperglycemia. This review aims to examine the effect of corticosteroids on increasing glucose in molecular levels based on literature studies. A literature searching was carried out on the PubMed, Science Direct, and Google Scholar databases published in 2010-2020. Corticosteroids can cause an increase in blood glucose levels by several mechanisms. In the liver, glucocorticoids increase endogenous plasma glucose and stimulate gluconeogenesis. Glucocorticoids increase the production of non-esterified fatty acids which affect the signal transduction of insulin receptor substrate-1 in skeletal muscle. In adipose, glucocorticoids increase lipolysis and visceral adiposity through increased transcription and expression of protein adipose triglyceride lipase and hormone-sensitive lipase. In pancreatic beta cells, glucocorticoids directly inhibit the beta cell response to glucose through the role of protein kinase B and protein kinase C. At the molecular level, corticosteroids can cause hyperglycemia through mechanisms in the liver, skeletal muscle tissue, adipose tissue, and pancreatic beta cells.

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Expression of hormone-sensitive lipase and its regulation by adrenaline in skeletal muscle

Biochemical Journal ◽

10.1042/bj3400459 ◽

1999 ◽

Vol 340 (2) ◽

pp. 459-465 ◽

Cited By ~ 91

Author(s):

Jozef LANGFORT ◽

Thorkil PLOUG ◽

Jacob IHLEMANN ◽

Michele SALDO ◽

Cecilia HOLM ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Soleus Muscle ◽

Lipase Activity ◽

Glycogen Phosphorylase ◽

Hormone Sensitive Lipase ◽

Dependent Protein Kinase ◽

Dependent Protein ◽

Hormone Sensitive ◽

Neutral Lipase

The enzymic regulation of triacylglycerol breakdown in skeletal muscle is poorly understood. Western blotting of muscle fibres isolated by collagenase treatment or after freeze-drying demonstrated the presence of immunoreactive hormone-sensitive lipase (HSL), with the concentrations in soleus and diaphragm being more than four times the concentrations in extensor digitorum longus and epitrochlearis muscles. Neutral lipase activity determined under conditions optimal for HSL varied directly with immunoreactivity. Expressed relative to triacylglycerol content, neutral lipase activity in soleus muscle was about 10 times that in epididymal adipose tissue. In incubated soleus muscle, both neutral lipase activity against triacylglycerol (but not against a diacylglycerol analogue) and glycogen phosphorylase activity increased in response to adrenaline (epinephrine). The lipase activation was completely inhibited by anti-HSL antibody and by propranolol. The effect of adrenaline could be mimicked by incubation of crude supernatant from control muscle with the catalytic subunit of cAMP-dependent protein kinase, while no effect of the kinase subunit was seen with supernatant from adrenaline-treated muscle. The results indicate that HSL is present in skeletal muscle and is stimulated by adrenaline via β-adrenergic activation of cAMP-dependent protein kinase. The concentration of HSL is higher in oxidative than in glycolytic muscle, and the enzyme is activated in parallel with glycogen phosphorylase.

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Regulation and role of hormone-sensitive lipase in rat skeletal muscle

Proceedings of The Nutrition Society ◽

10.1079/pns2004359 ◽

2004 ◽

Vol 63 (2) ◽

pp. 309-314 ◽

Cited By ~ 16

Author(s):

Morten Donsmark ◽

Jozef Langfort ◽

Cecilia Holm ◽

Thorkil Ploug ◽

Henrik Galbo

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Energy Content ◽

Hormone Sensitive Lipase ◽

Fibre Types ◽

Muscle Fibre Types ◽

Muscle Fibres ◽

Energy Store ◽

Hormone Sensitive ◽

Neutral Lipase

Intramyocellular triacylglycerol (TG) is an important energy store, and the energy content of this depot is higher than the energy content of the muscle glycogen depot. It has recently been shown that the mobilization of fatty acids from this TG pool may be regulated by the neutral lipase hormone-sensitive lipase (HSL). This enzyme is known to be rate limiting for intracellular TG hydrolysis in adipose tissue. The presence of HSL has been demonstrated in all muscle fibre types by Western blotting of muscle fibres isolated by collagenase treatment or after freeze-drying. The content of HSL varies between fibre types, being higher in oxidative fibres than in glycolytic fibres. When analysed under conditions optimal for“ HSL, neutral lipase activity in muscle can be stimulated by adrenaline as well as by contractions. These increases are abolished by the presence of anti-HSL antibody during analysis. Moreover, immunoprecipitation with affinity-purified anti-HSL antibody causes similar reductions in muscle HSL protein concentration and in measured neutral lipase responses to contractions. The immunoreactive HSL in muscle is stimulated by adrenaline via β-adrenergic activation of cAMP-dependent protein kinase (PKA). From findings in adipocytes it is likely that PKA phosphorylates HSL at residues Ser563, Ser659and Ser660. Contraction probably also enhances muscle HSL activity by phosphorylation, because the contraction-induced increase in HSL activity is elevated by the protein phosphatase inhibitor okadaic acid and reversed by alkaline phosphatase. A novel signalling pathway in muscle by which HSL activity may be stimulated by protein kinase C (PKC) via extracellular signal-regulated kinase (ERK) has been demonstrated. In contrast to previous findings in adipocytes, in muscle the activation of ERK is not necessary for stimulation of HSL by adrenaline. However, contraction-induced HSL activation is mediated by PKC, at least partly via the ERK pathway. In fat cells ERK is known to phosphorylate HSL at Ser600. Hence, phosphorylation of different sites may explain the finding that in muscle the effects of contractions and adrenaline on HSL activity are partially additive. In line with the view that the two stimuli act by different mechanisms, training increases contraction-mediated HSL activation but diminishes adrenaline-mediated HSL activation in muscle. In conclusion, HSL is present in skeletal muscle and can be activated by phosphorylation in response to both adrenaline and muscle contractions. Training increases contraction-mediated HSL activation, but decreases adrenaline-mediated HSL activation in muscle.

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Effect of Pleurotus Ostreatus on Pancreatic Beta Cells of Diabetes Mellitus Mice Model

JURNAL ILMU KEFARMASIAN INDONESIA ◽

10.35814/jifi.v15i2.507 ◽

2017 ◽

Vol 15 (2) ◽

pp. 155 ◽

Cited By ~ 1

Author(s):

Ningrum Wahyuni ◽

Syafrudin Ilyas ◽

Alya Amila Fitrie

Keyword(s):

Diabetes Mellitus ◽

Blood Glucose ◽

Beta Cells ◽

Pleurotus Ostreatus ◽

Pancreatic Beta Cells ◽

Low Dose ◽

Ethanol Extract ◽

Glucose Levels ◽

Blood Glucose Levels ◽

One Way Anova

Over the last 30 years, the number of people suffering from diabetes mellitus has doubled globally. Adipose tissue dysfunction plays an important role in insulin resistance. Mushroom has been traditionally used to prevent diabetes. This research aims to study the anti-oxidative effect of Pleurotus ostreatus on pancreatic beta cells. This study is an experimental posttest only control group design. The subjects were 24 male wistar mice, divided into six groups. Group P0 was given distilled water and citrate buffer. Group P1 was given high fat diet (HFD) and low dose streptozotocin (STZ). Group P2 and 3 were given HFD and low dose STZ along with Pleurotus ostreatus ethanol extract. Group P4 and P5 were given HFD and low dose STZ, and then given Pleurotus ostreatus ethanol extract. Blood glucose levels and pancreatic beta cells area count were done after treatment. Data obtained was analyzed using one-way ANOVA test. One-way ANOVA test showed signifi cant difference in all the groups (p<0.05). Post Hoc test results showed difference in blood glucose levels and pancreatic beta cells area count. Pleurotus ostreatus ethanol extract can prevent cellular damage to murine pancreatic beta cells but unable to reverse the damage to the beta cells.

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SEL BETA PANKREAS SINTESIS DAN SEKRESI INSULIN

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.4.3.2012.795 ◽

2013 ◽

Vol 4 (3) ◽

Author(s):

Eka Banjarnahor ◽

Sunny Wangko

Keyword(s):

Insulin Secretion ◽

Blood Glucose ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Plasma Membranes ◽

Secretory Granules ◽

Chromosome 11 ◽

Insulin Synthesis ◽

Glucose Levels ◽

Blood Glucose Levels

Abstract: Insulin synthesis and secretion are done by pancreatic beta cells. Preceding the insulin synthesis, there is a gen translation in chromosome 11 that produces insulin, packed in secretory granules. Insulin secretion is induced by the alteration of blood glucose levels, resulting in the occurence of intracellular reactions preceded by changes of ATP/ADP ratios that trigger the depolarisation of plasma membranes. Furthermore, extracellular Ca2+ ions move inward to beta cells to activate exocytosis. There are still many unknown problems so far in either the synthesis or secretion of insulin that cause unfulfilled insulin needs in the body.Keywords: beta cells, insulin, synthesis, secretionAbstrak: Sintesis dan sekresi insulin dilakukan oleh sel beta pankreas. Sintesis insulin diawali oleh salinan gen pada kromosom 11, yang akan menghasilkan insulin, di kemas di dalam granul-granul sekretorik. Sekresi insulin diinduksi oleh perubahan kadar glukosa, yang berakibat terjadinya reaksi intrasel yang diikuti adanya perbedaan rasio ATP/ADP yang memicu reaksi depolarisasi membran plasma. Sebagai akibat lanjut Ca2+ ekstrasel akan masuk ke dalam sel beta yang berfungsi mengaktifkan eksositosis. Sampai saat ini masih banyak ditemui masalah baik dalam hal sintesis maupun sekresi insulin yang mengakibatkan kebutuhan insulin tubuh tidak terpenuhi.Kata kunci: sel beta, insulin, sintesis, sekresi

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Protein kinase A-dependent stimulation of exocytosis in mouse pancreatic beta-cells by glucose-dependent insulinotropic polypeptide

Diabetes ◽

10.2337/diabetes.46.4.615 ◽

1997 ◽

Vol 46 (4) ◽

pp. 615-621 ◽

Cited By ~ 22

Author(s):

W. G. Ding ◽

J. Gromada

Keyword(s):

Protein Kinase ◽

Protein Kinase A ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Kinase A ◽

Stimulation Of

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Faculty Opinions recommendation of Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1047341.497281 ◽

2006 ◽

Author(s):

Gourisankar Ghosh

Keyword(s):

Endoplasmic Reticulum ◽

Protein Kinase ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Insulin Biosynthesis

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Vanadyl Sulfate Treatment Stimulates Proliferation and Regeneration of Beta Cells in Pancreatic Islets

Journal of Diabetes Research ◽

10.1155/2014/540242 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 15

Author(s):

Samira Missaoui ◽

Khémais Ben Rhouma ◽

Mohamed-Tahar Yacoubi ◽

Mohsen Sakly ◽

Olfa Tebourbi

Keyword(s):

Blood Glucose ◽

Insulin Sensitivity ◽

Pancreatic Islets ◽

Beta Cells ◽

Control Level ◽

Diabetic Rats ◽

Diabetic Group ◽

Dependent Manner ◽

Glucose Levels ◽

Blood Glucose Levels

We examined the effects of vanadium sulfate (VOSO4) treatment at 5 and 10 mg/kg for 30 days on endocrine pancreas activity and histology in nondiabetic and STZ-induced diabetic rats. In diabetic group, blood glucose levels significantly increased while insulinemia level markedly decreased. At the end of treatment, VOSO4at a dose of 10 mg/Kg normalized blood glucose level in diabetic group, restored insulinemia, and significantly improved insulin sensitivity. VOSO4also increased in a dose-dependent manner the number of insulin immunopositive beta cells in pancreatic islets of nondiabetic rats. Furthermore, in the STZ-diabetic group, the decrease in the number of insulin immunopositive beta cells was corrected to reach the control level mainly with the higher dose of vanadium. Therefore, VOSO4treatment normalized plasma glucose and insulin levels and improved insulin sensitivity in STZ-experimental diabetes and induced beta cells proliferation and/or regeneration in normal or diabetic rats.

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The Potency of Senggani (Melastoma malabathricum L) Leaves in Repair of Pancreatic Beta Cells for Diabetes Mellitus Patients: A Narrative Review

Current Biochemistry ◽

10.29244/cb.7.2.3 ◽

2020 ◽

Vol 7 (2) ◽

pp. 61-70

Author(s):

Galuh Rizal Prayoga ◽

Aziz Syamsul Huda ◽

Syndilona Br Sitepu

Keyword(s):

Diabetes Mellitus ◽

Binding Site ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Docking Simulation ◽

The Body ◽

Inhibition Mechanism ◽

Active Compounds ◽

Glucose Levels ◽

Melastoma Malabathricum

Diabetes mellitus is often caused by damage to pancreatic beta cells which play a role in secreting insulin in the body. Damage to pancreatic beta cells causes the body to lack insulin. Dipeptidyl peptidase-4 (DPP-4) is a peptidase enzyme complex located on the surface of the cell membrane. Inhibition of the DPP4 enzyme will increase blood GLP-1 levels and induce regeneration of pancreatic beta cells. Senggani leaf (Melastoma malabathricum) boiled water is believed by the people of the Ciamis area to be used as a diabetes medicine. There have been many studies and reviews related to Senggani (Melastoma malabathricum) and its potential. This review focuses on the discussion of Senggani as an antidiabetic by analyzing the reduction in glucose levels and the repair ability of pancreatic beta cells. The results of the literature study that show that senggani leaves have the ability to reduce blood glucose levels and repair activity of pancreatic beta cells through the DPP-4 enzyme inhibition mechanism supported by molecular docking simulation data. There are 12 active compounds that have a binding site similarity above 50% with the comparison compound vildagliptin. Rutin is the best active compound which has a 100% similarity of the binding site. Based on in vivo research and toxicity analysis on the admetsar database, senggani leaf extract and active compounds of senggani leaves have low toxicity, making it safe to be used as antidiabetic herbal preparations.

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