This document provides information about the July 2013 issue of Biomed, the newsletter of the Department of Biochemistry at Adichunchanagiri Institute of Medical Sciences. It discusses the retirement of a senior technician after 25 years of service and the expansion of department facilities. It also announces the MCI grant for increased undergraduate admissions and approval of university status for the institution. Short articles summarize research on Saposin B deficiency, Irisin, Sirtuins, Visfatin, and provide a crossword puzzle related to biochemical bases of diseases.
Revisiting Caloric Restriction as Therapeutic Strategy for MetS, T2DM and Obe...Vinod Nikhra
OVERNUTRITION AND ADIPOSITY: Overnutrition contributes to chronic energy surplus leading to adiposity, IR, MetS and obesity with its fallouts including increased oxidative stress, altered glucose, fat and protein metabolism, and altered skeletal muscle mitochondrial function.
REDOX BALANCE AND THIOREDOXIN SYSTEM: The cellular redox balance is regulated by activity of several antioxidant systems including TXN system. TNX is a key player in regulation of glucose homeostasis and lipid metabolism. The overexpression of TXNIP in T2DM, MetS and obese subjects is associated with metabolic abnormalities including apoptosis of β-cells, decreased insulin sensitivity and energy expenditure. The reduced oxidative capacity of skeletal muscle leads to accumulation of IMTG and affects mitochondrial function. TXNIP influences metabolic regulation mainly through insulin release from β-cells, glucose production from liver and glucose uptake in peripheral tissues. In addition, it acts as a nutrient sensor in discrete regions of brain.
EFECTS OF CR ON METABOLIC HOMEOSTASIS: CR is a potentially effective therapeutic strategy to improve adiposity and insulin sensitivity at tissue level. CR associated weight loss decreases IMTG and improves mitochondrial function in skeletal myocytes. The decrease in adipose mass, oxidative stress and inflammation lead to downregulation of TXNIP, eliminating its inhibitory effect on glycolysis, glucose transporters, insulin receptors and receptor substrate, insulin-stimulated Akt activation and PI3K.
CONCLUSION - NOVEL ADDITIVES TO POLYPHARMACY: The CR consistently leads to improved cardiometabolic outcomes and exerts beneficial effects on every organ system. Yet, CR is difficult to implement in practice for multiple reasons. Still, the focus on CR is important within a specific disease context to clearly delineate underlying mechanisms and exploit the research to achieve therapeutic goals. TXNIP is a potential therapeutic target. Anti-diabetic agents like metformin, GLP-1 agonists and CRMs like resveratrol inhibit TXNIP expression. Verapamil – a calcium channel blocker, tranilast - a tryptophan metabolite and allopurinol reduce TXNIP levels in vivo and in vitro studies. Lowering TXNIP levels halts β-cells apoptosis. On a cautious note, the loss of TXNIP may have serious consequences as TXNIP expression is required for maintaining normal fasting glycaemia and TXNIP being a tumour suppressor, its loss is associated with increased incidence of cancer.
Final Presentation for Block 6
Objectives:
Describe the mechanism of action, side-effects and counseling points for GLP-1 RA
Compare and contrast GLP-1 RA studies
Discuss the PIONEER-6 study and its implications to clinical practice
COMPARATIVE ASSESSMENT OF THE EEFFECT OF ARGINASE INHIBITOR L-NORVALINE AND M...ShubhamBaliyan13
Having metabolic syndrome can induce the risk of developing especially Type 2 Diabetes, insulin resistance , Atherosclerosis, cardiovascular disease, visceral Obesity, Dyslipidemias.
This study aimed at determining the prevalence of metabolic syndrome ( MetS) and its individual components and the most critical predictive risk factors of MetS in Type 2 Diabetes .
Our aim is to reduce morbidity and mortality related to Non communicable diseases such as hypertension, diabetes, cardiovascular disease, stroke, Obesity, Cancer and lifestyle diseases among those least able to withstand the burden of the disease.
Slide Presentation
Diabetes Melliuts Type 2 management basics are life style modifications followed by use of Metformin
What is the best and safest next pharmacologic choice
Revisiting Caloric Restriction as Therapeutic Strategy for MetS, T2DM and Obe...Vinod Nikhra
OVERNUTRITION AND ADIPOSITY: Overnutrition contributes to chronic energy surplus leading to adiposity, IR, MetS and obesity with its fallouts including increased oxidative stress, altered glucose, fat and protein metabolism, and altered skeletal muscle mitochondrial function.
REDOX BALANCE AND THIOREDOXIN SYSTEM: The cellular redox balance is regulated by activity of several antioxidant systems including TXN system. TNX is a key player in regulation of glucose homeostasis and lipid metabolism. The overexpression of TXNIP in T2DM, MetS and obese subjects is associated with metabolic abnormalities including apoptosis of β-cells, decreased insulin sensitivity and energy expenditure. The reduced oxidative capacity of skeletal muscle leads to accumulation of IMTG and affects mitochondrial function. TXNIP influences metabolic regulation mainly through insulin release from β-cells, glucose production from liver and glucose uptake in peripheral tissues. In addition, it acts as a nutrient sensor in discrete regions of brain.
EFECTS OF CR ON METABOLIC HOMEOSTASIS: CR is a potentially effective therapeutic strategy to improve adiposity and insulin sensitivity at tissue level. CR associated weight loss decreases IMTG and improves mitochondrial function in skeletal myocytes. The decrease in adipose mass, oxidative stress and inflammation lead to downregulation of TXNIP, eliminating its inhibitory effect on glycolysis, glucose transporters, insulin receptors and receptor substrate, insulin-stimulated Akt activation and PI3K.
CONCLUSION - NOVEL ADDITIVES TO POLYPHARMACY: The CR consistently leads to improved cardiometabolic outcomes and exerts beneficial effects on every organ system. Yet, CR is difficult to implement in practice for multiple reasons. Still, the focus on CR is important within a specific disease context to clearly delineate underlying mechanisms and exploit the research to achieve therapeutic goals. TXNIP is a potential therapeutic target. Anti-diabetic agents like metformin, GLP-1 agonists and CRMs like resveratrol inhibit TXNIP expression. Verapamil – a calcium channel blocker, tranilast - a tryptophan metabolite and allopurinol reduce TXNIP levels in vivo and in vitro studies. Lowering TXNIP levels halts β-cells apoptosis. On a cautious note, the loss of TXNIP may have serious consequences as TXNIP expression is required for maintaining normal fasting glycaemia and TXNIP being a tumour suppressor, its loss is associated with increased incidence of cancer.
Final Presentation for Block 6
Objectives:
Describe the mechanism of action, side-effects and counseling points for GLP-1 RA
Compare and contrast GLP-1 RA studies
Discuss the PIONEER-6 study and its implications to clinical practice
COMPARATIVE ASSESSMENT OF THE EEFFECT OF ARGINASE INHIBITOR L-NORVALINE AND M...ShubhamBaliyan13
Having metabolic syndrome can induce the risk of developing especially Type 2 Diabetes, insulin resistance , Atherosclerosis, cardiovascular disease, visceral Obesity, Dyslipidemias.
This study aimed at determining the prevalence of metabolic syndrome ( MetS) and its individual components and the most critical predictive risk factors of MetS in Type 2 Diabetes .
Our aim is to reduce morbidity and mortality related to Non communicable diseases such as hypertension, diabetes, cardiovascular disease, stroke, Obesity, Cancer and lifestyle diseases among those least able to withstand the burden of the disease.
Slide Presentation
Diabetes Melliuts Type 2 management basics are life style modifications followed by use of Metformin
What is the best and safest next pharmacologic choice
This presentation illustrates the various pathways of development of AD ,including the recent molecular pathways , and their implication in early diagnosis and therapy .
Resveratrol, Caloric Restriction and Longevity in Human Mitochondrial Dysfunc...Ayetenew Abita Desa
Caloric restriction and the phytoalexin resveratrol found to increase longevity and decrease aging. This is the summary I have made after extensive review. everybody is invited to comment on it.
Glucagon like peptide-1 (GLP-1) is an incretin secretory molecule. GLP-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes (T2DM) due to their attributes such as body weight loss, protection of islet β cells, promotion of islet β cell proliferation and minimal side effects. Studies have found that GLP-1R is widely distributed on pancreatic and other tissues and has multiple biological effects, such as reducing neuroinflammation, promoting nerve growth, improving heart function, suppressing appetite, delaying gastric emptying, regulating blood lipid metabolism and reducing fat deposition. Moreover, GLP-1RAs have neuroprotective, anti-infectious, cardiovascular protective, and metabolic regulatory effects, exhibiting good application prospects. Growing attention has been paid to the relationship between GLP-1RAs and tumorigenesis, development and prognosis in patient with T2DM. Here, we reviewed the therapeutic effects and possible mechanisms of action of GLP-1RAs in the nervous, cardiovascular, and endocrine systems and their correlation with metabolism, tumours and other diseases.
Mucopolysaccharidosis type II MPS II or Hunter syndrome is Metabolism by lysosomal accumulation with a recessive inheritance pattern associated with the X chromosome. It is caused by lack of activity of the lysosomal enzyme iduronate 2 sulfatase, encoded by the IDS gene. Plasma iduronate 2 sulfatase enzymatic activity was measured and the IDS gene in genomic DNA was analyzed by automated direct sequencing. The enzyme activity was 1.2 mol l h reference value 2 mol l h and molecular analysis detected the mutation c.1403G A p.R468Q , confirming the diagnosis of MPS II. rice field. In conclusion, there are few groups dedicated to this disease family here in Mexico, highlighting the need to form an expert team of physicians and scientists dedicated to inborn errors of metabolism to stay up to date. Miss. Parimala L | Babu M "Hunter Syndrome: A Case Report" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-7 | Issue-1 , February 2023, URL: https://www.ijtsrd.com/papers/ijtsrd52814.pdf Paper URL: https://www.ijtsrd.com/medicine/other/52814/hunter-syndrome-a-case-report/miss-parimala-l
1. Adichunchanagiri
Institute of Medical
Sciences
Chief Patron
Paramapoojya
Sri Sri Sri
Nirmalanandanatha
Mahaswamiji
Chief Advisor
Dr Shivaramu M.G.
Principal A.I.M.S.
Chief Editor
Dr Aliya Nusrath.
Professor & Head
Dept. of Biochemistry
Editorial Board
Dr. Rajeshwari A.
Assoc. Professor
Sri. Somashekar G.N.
Asst. Professor
Dr. Chikkanna D.
Asst. Professor
Dr Maithri C.M.
Asst. Professor
Dr Asha Rani N.
Asst. Professor
Members
Dr. Prathibha K.
Tutor cum PG
Dr Namitha D.
Tutor cum PG
Contact information:
biomedaims@gmail.com
Biomed
Dept of Biochemistry
___________________________________________________
News letter
VOLUME 1 ISSUE 3 JULY 2013
___________________________________________________
From Editor’s Desk
Greetings
With immense pleasure we are releasing the third
issue of Biomed. Medical field is ever growing with newer
trends. In this context we have tried to throw light on newer
protein frontiers in health and disease in this edition.
Many a changes have taken place in the department.
It was disheartening to let go of our senior technician Sri
Mahalinge Gowda after 25 years of his service. However as
it is said life goes on, we also had many a cause for
celebration. Our department was expanded with newly
furnished research laboratory and other facilities. Also we
congratulate and welcome the MCI grant for 150
admissions of undergraduates as well as the Government
approval of University status to our institution.
Send off party of Sri Mahalinge Gowda
First Row (From left to right): Dr Asha Rani,
Dr Maithri, Dr Rajeshwari A, Sri Mahalinge Gowda,
Dr Aliya Nusrath, Sri Somashekhar and
Dr Chikkanna
Second Row (From left to right): Sri Hongere Gowda, Sri
Yateesh, Sri Mahalinge Gowda,
Sri Ramesh, Sri Shankare Gowda and Sri Krishne Gowda
2. Saposin B deficiency
Arylsulfatase A deficiency results in Metachromatic leukodystrophy (MLD). There are three clinical
subtypes, which are primarily distinguished by age of onset, late-infantile MLD (50-60%), juvenile
MLD(20-30%) and adult MLD (15-20%). MLD is suspected in individuals with progressive neurological
functions and MRI evidence of leucodystrophy. MLD may be due to ARSA enzyme activity in leucocytes
less than 10% of normal controls. However assay of ARSA enzyme activity cannot distinguish between
MLD and ARSA pseudodeficiency, where ARSA enzyme activity is 5% to 20% of normal controls and does
not cause MLD. Thus the diagnosis of MLD must be confirmed by one or more tests like molecular testing
of the ARSA, the only gene in which mutation causes ARSA deficiency, urinary excretion of sulfatides and
presence of metachromatic lipid deposit in nervous tissue.
High prevalence of ARSA pseudodeficiency with low levels of ARSA enzyme activity is found in
association with many disorders and it is diagnosed with the neurodegenerative disorder is often consider
due to deficiency of ARSA activity. However schizophrenia depression, substance abuse, multiple sclerosis
and various forms of dementia frequently seen in general population may not be due to the low levels of
ARSA activity.
Saposin B is an activator protein, is required for the degradation of sulfatide by Arylsulfatase A
(ARSA) and hydrolysis of globotriaosylceramide and digalactosylceramide by α-galactosidases. Saposins
(A, B, C and D) are small glycoprotiens derived from the precursor protein prosaposin by proteolytic
cleavage. Prosaposin is 65-70KDa protein exists both as secretory protein as well as integral membrane
protein and as neurotropic activities. Deficiency of saposin due to gene defect results in the accumulation of
multiple sphingolipids leading to the complex sphingolipidosis with early fatal consequences. Saposin B
deficiency causes MLD like disorder due to the disrupted glycolipid degradation, MLD like clinical
presentation leukodystrophy on MRI, normal ARSA enzyme activity and excess urinary sulfatide excretion
or sulfatide storage. Diagnosis can be evaluated on depressed sulfatide degradation by culture cells,
immunochemical assessment of saposin B levels or sequence analysis of gene encoding saposin B.
Dr. Rajeshwari A Assoc. Professor, Biochemistry
Irisin
The benefit of exercise has been extensively studied and is the method for non-pharmacological
treatment of cardiovascular and metabolic diseases like diabetes mellitus, obesity etc. Exercise is known to
induce weight loss and improve glucose homeostasis. However, the molecular mechanism behind it
remained largely unexplained. In 2012, a hormone called Irisin named after Greek goddess iris, was
discovered by Bruce M Spigelmen et al which was found to be responsible for exercise induced weight loss
and improved glucose homeostasis. It is a PGC - 1α induced myokine, a 112 AA polypeptide secreted from
muscle into the bloodstream in response to exercise.
There are two types of adipose tissues in our body namely, white adipose tissue and brown adipose
tissue. The main function of white adipose tissue is to store fat whereas brown adipose tissue has non
shivering thermogenic properties due to expression of uncoupling protein – 1 and increased mitochondrial
content.
As per the molecular mechanism, exercise is the stimulus for release of PGC1α which is a co-
activator of PPAPγ (peroxisome proliferator activated receptor). This in turn stimulates the expression of
FNDC5 which in turn is proteolytically cleaved to release the active hormone Irisin. This Irisin has cell
surface receptors. It increases the expression of UCP1 and cidea mRNA, which causes the browning of
primarily subcutaneous and also of visceral adipose tissue and thereby inducing thermogenesis. So Irisin
causes white adipose tissue to get converted to brown adipose tissue and thereby reduction of insulin
resistance and improvement of glucose homeostasis. Hence it may be useful as anti-obesity treatment and
anti-diabetic treatment. Hence Irisin may be useful in the treatment of obesity, diabetes and metabolic
syndrome especially to people who cannot exercise because of physical limitations.
At present, all the effects of Irisin are seen in mice, because of its 100% sequence homology, it is
being assumed to have same effect in humans for whom clinical trials are being conducted.
Dr. Maithri C.M, Assistant Professor, Biochemistry
3. Sirtuin or Sir2 proteins
Sirtuin or Sir2 proteins are a class of proteins that possess either mono-ribosyltransferase, or deacylase
activity. The name Sir2 comes from the yeast gene 'silent mating-type information regulation 2',the gene
responsible for cellular regulation in yeast. Sirtuins have been implicated in influencing a wide range of
cellular processes like aging, transcription, apoptosis, inflammation and stress resistance, as well as energy
efficiency and alertness during low-calorie situations. Sirtuins can also control circadian clocks and
mitochondrial biogenesis. Mammals possess seven sirtuins (SIRT1-7) that occupy different subcellular
compartments such as the nucleus (SIRT1, -2, -6, -7), cytoplasm (SIRT1 and SIRT2) and the mitochondria
(SIRT3, -4 and -5).
Clinical significance
Sirtuin activity is inhibited by nicotinamide, which binds to a specific receptor site, so it is thought that
drugs that interfere with this binding should increase sirtuin activity. Development of new agents that would
specifically block the nicotinamide-binding site could provide an avenue for development of newer agents to
treat degenerative diseases such as cancer, Alzheimer's, diabetes, atherosclerosis, and gout.
Alzheimer's disease: SIRT1 deacetylates and coactivates the retinoic acid receptor beta that upregulates the
expression of alpha-secretase (ADAM10). Alpha-secretase in turn suppresses beta-amyloid production.
Furthermore, ADAM10 activation by SIRT1 also induces the Notch signaling pathway, which is known to
repair neuronal damage in the brain.
Aging: Preliminary studies with resveratrol, a possible SIRT1 activator, have led some scientists to
speculate that resveratrol may extend lifespan. Further experiments conducted by Rafael de Cabo et al.
showed that resveratrol-mimicking drugs such as SRT1720 could extend the lifespan of obese mice by 44%.
Comparable molecules are now undergoing clinical trials in humans.
Dr. Asha Rani N, Assistant Professor, Biochemistry
Visfatin
Visfatin is a newly discovered adipocyte hormone with a direct relationship between plasma visfatin level
and type 2 diabetes mellitus. Also known as Nicotinamide phosphoribosyltransferase (NAmPRTase or
Nampt) as pre-B-cell colony-enhancing factor 1 (PBEF1) .It is an enzyme that in humans is encoded by the
PBEF1 gene. This protein has also been reported to be a cytokine (PBEF) that promotes B cell maturation
and inhibits neutrophil apoptosis.
NAmPRTase catalyzes the following chemical reaction:
Nicotinamide D-ribonucleotide + diphosphate -------Nicotinamide + 5-phospho-alpha-D-ribose 1-
diphosphate
This enzyme belongs to the family of glycosyltransferases, to be specific, the pentosyltransferases. This
enzyme participates in nicotinate and nicotinamide metabolism.
Function: The protein is an adipokine that is localized to the bloodstream It is an endocrine, autocrine as
well as paracrine peptide with many functions including enhancement of cell proliferation, biosynthesis of
nicotinamide mono- and dinucleotide and hypoglycaemic effect, including the promotion of vascular smooth
muscle cell maturation and inhibition of neutrophil apoptosis. It also activates insulin receptor and has
insulin-mimetic effects, lowering blood glucose and improving insulin sensitivity. Visfatin binds to the
insulin receptor at a site distinct from that of insulin and causes hypoglycaemia by reducing glucose release
from liver cells and stimulating glucose utilization in adipocytes and myocytes. The protein is highly
expressed in visceral fat and serum levels of the protein correlate with obesity. This has also been identified
in many tissues and organs including the brain, kidney, lung, spleen and testis but preferentially expressed in
visceral adipose tissue Visfatin is up regulated by hypoxia, inflammation and hyperglycaemia and
downregulated by insulin, somatostatin and statins.
Dr.Prathibha K Postgraduate, Biochemistry
4. Fun and Learn
Biomed Crossword
(Crossword on biochemical basis of diseases)
1 2 3 4 5
6 7
8 9
10
11 12 13
14 15
16 17
18
19 20 21
22
23
24
Across
1. X-linked Mucopolysacchroidosis (7)
7. Disease due to trinucleotide CAG expansion (6)
8. A disease common in hilly areas (6)
11. Also called as Forbe’s disease (5)
12. An underlying disease for all organ complications (8)
16. A disease with four D’s (8)
18. After the age of 40 years, you need to watch for this
disease (5)
20. ___ syndrome in which there is hypoglycaemia and
dicarboxylic aciduria in infants (4) (Abbreviation)
22. A disease due to protein misfolding (5)
23. A disease with burnt sugar urine (4) (Abbreviation)
24. Accumulation of GM2 occurs in this disease (3,5)
Down
2. ___ syndrome with trisomy 18
3. First disease with gene therapy (4)
(Abbreviation)
4. Many great personalities Newton,
Darwin etc suffered from this disease
(4)
5. A disease which is pronoun for
women (4)
6. A disease with charlie chaplin gait
(14)
9. Phosphofructokinase deficiency
disease (6)
10. A group of sexually transmitted
diseases (3)
13. Limeys did not suffer from this
disease (6)
14. β- Glucoronidase deficiency (4)
15. A primary dyslipoproteinemis
with low HDL (7)
16. Nutritional disorders (3)
(Abbreviation)
17. Dietary consumption of
methylated fatty acids leads to this
neurological disorder (7)
19. _______ eye disease (4)
21. About 20 % inmates of lunatic
asylum may have this disease (3)
(Abbreviation)
By Dr Aliya Nusrath
Prof and HOD, Biochemistry.
Answers will be given in next
issue
{Answers of previous issue
Across: 2.Collgen 7.Uracil. 9. BAL 10 Page
11.ETC 12.Ligase 13.Iodine 14.CO 15.Ryle
16.Laminin 19.Niacin 21.Leptin 23.STD
24.Peptide 25.Orotate 27.Starch 29.RE
30.Myosin 31.Phenol
Down: 1.Fiber 2.Calcium 3.Lipid 4.Arginine
5.Nucleotide 6.Sanger 8.Insulin 17.Acetone
18.Intron 19.NTP 20.Citrate 22.NSAIDs
26.Exon 27.SNP 2
QUOTE
“Research is to see what everybody has seen and to think what nobody else has thought”.
Albert Szent-Gyorgyi.