1. Seminar
on
ADIPONECTIN : AS A
BIOMARKER IN DIABETES
Presented by
Anoop tiwari
Roll no. 395
Dept. of pharmacy practice
Niper, Hajipur
2. CONTENTS
• Introduction
• Burden of the disease
• Obesity
• Adipokines
• Adipose tissue as an endocrine organ
• Various adipokines
• Adiponectin
• Adiponectin as a hormone
• Adiponectin receptors
• Conclusion
3. •Type 2 DM more typically develops with increasing age but is now
being diagnosed more frequently in children and young adults,
particularly in obese adolescents.
INTRODUCTION
4. Burden of the Disease
• Around 7% of Indian Adults
• Most of the world’s Diabetics dwell in India
5. Obesity
•Obesity results from an imbalance between lipogenesis (fat
synthesis) and lipolysis (fat destruction).
•Lipogenesis which occurs in liver and adipose tissue involves
fatty acid synthesis followed by triglyceride synthesis.
8. Adipose tissue
•Adipose tissue or fat is loose connective tissue composed of
adipocytes. Its main role is to store energy in the form of fat,
although it also cushions and insulates the body.
•Two types of adipose tissue exist : white adipose tissue (WAT) and
brown adipose tissue (BAT).
9. Anatomical features
•In humans, adipose tissue is located beneath the skin
(subcutaneous fat), and is also found around internal organs
(visceral fat). Adipose tissue is found in specific locations which
are referred to as “adipose depots”.
10. Fat cells
Adipose cells store majority of the body’s fat, vary in size and
number.
Increase in body fatness is due to:
• Fat cell hypertrophy
•Fat cell hyperplasia
11. Adipose tissue as an endocrine organ
•Adipose tissue has come into focus as an endocrine organ.
•Adipose tissue secretes a variety of bioactive peptides (adipokines).
•Adipokines may locally regulate fat mass by modulating adipocyte
size/number or angiogenesis and inversely increased fat mass leads
to dysregulation of adipocyte functions.
Various adipokines
• Adiponectin
• Leptin
• Resistin
• Adipsin
• Apelin
•Visfatin
• Vaspin
• Omentin
• Lipocalin-2
15. History
• Adiponectin was first identified in 1995 in differentiating
adipocytes.
• In 1996 it was identified in mice as the mRNA transcript most
highly expressed in adipocytes.
• In 2007, adiponectin was identified as a transcript highly
expressed in pre-adipocytes (precursors of fat cells) differentiating
into adipocytes.
Introduction
Adiponectin is a protein which in humans is encoded by the
ADIPOQ gene.
• Composed of 247 amino acids.
• Accounts for 0.05 % of total serum protein.
• Concentration: 2- 20 μg/mL in the blood.
• Adiponectin also gaining recognition as a hormone.
16. Adiponectin as a hormone
•Adiponectin is a white and brown adipose tissue hormone.
•Circulates in the bloodstream in trimeric, hexameric, and
high molecular-mass species.
•Adiponectin is an insulin sensitizing hormone that exerts its
action through its receptors AdipoR1, AdipoR2 & T-cadherin.
•Adiponectin enhances AMPK (5-adenosine monophosphate-
activated protein kinase) and the PPARα pathway in the liver
and skeletal muscle.
•Adiponectin can exist in two different forms as-
1. A full-length protein.
2. A globular form.
•The globular form of adiponectin appears to stimulate β
oxidation in muscle.
17. Why is it important to study adiponectin?
•Evidence strongly suggests that adiponectin plays a role in the
pathophysiology of type 2 diabetes and other metabolic syndrome
diseases.
18. Correlation between adiponectin and insulin
resistance
•Obesity and type 2 diabetes are associated with decreased
adiponectin levels.
•Reduced plasma adiponectin is also seen in people with
conditions such as cardiovascular disease and hypertension,
diseases that are often associated with insulin resistance.
•Adiponectin is inversely proportional to obesity, diabetes and
other insulin-resistant states.
•Plasma concentrations reveal a dimorphism, with females having
higher levels than males.
19. •Adiponectin increases fatty acids oxidation, which lowers
circulating free fatty acids and prevents insulin resistance.
•Adiponectin has been reported to exert an anti-atherosclerotic
effect.
•It inhibits macrophage activation and foam cell accumulation,
while it also augments endothelial nitrous oxide production and
protects the vasculature by reducing platelet aggregation and
vasodilation.
•Apart from causing metabolic dysfunction, adiponectin deficiency
may also contribute to coronary heart disease, insulin resistance,
nonalcoholic fatty liver disease.
20. •The physiological role of adiponectin has not yet been fully
elucidated, but it is believed that it has the ability to reduce
glucose, triglycerides, and free fatty acids.
•It plays a major role in the pathogenesis of metabolic syndrome.
•Metabolic syndrome comprises a cluster of metabolic disorders
that give rise to such metabolic risk factors.
•Such as visceral obesity, insulin resistance, hyperglycaemia,
dyslipidaemia, and hypertension.
21. Adiponectin receptors
• There are two known ones: AdipoR1 and AdipoR2 & Tcadherin.
• They are integral membrane proteins that have seven
transmembrane domains where the N terminus is located within the
cell, and the C terminus is external.
• AdipoR1 is a receptor that mainly binds globular adiponectin,
while AdipoR2 binds to full-length adiponectin.
• AdipoR1 is abundant in skeletal muscle. On the other hand,
AdipoR2 is most expressed in the liver.
• T-cadherin can bind to the hexameric and HMW forms of
adiponectin but not to monomer globular and trimeric forms.
• T-cadherin is ubiquitously expressed, with the highest expression
found in the heart and the aortic, carotid, iliac, and kidney arteries.
23. CONCLUSION
Adiponectin is a potent insulin sensitizing molecule.
The two forms (globular and full-length) bind to different
receptors and have different effects.
Decreased levels of adiponectin induced by genetic mutations,
obesity, and high fat diets lead to insulin resistance and
pathological conditions such as type 2 diabetes.
Adiponectin activates signaling cascades that eventually increase
glucose uptake by muslce, increase fatty acid oxidation by muscle
and liver, and decrease gluconeogenesis in the liver.
In the future, Osmotin could be used as a novel therapeutic
method for hypoadiponectinemia.
24. •Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y,
Matsubara K(1996)."cDNA cloning and expression of a novel
adipose specific collagen-like factor, apM1 (AdiPose Most
abundant Gene transcript 1)". Biochem. Biophys. Res. Commun.
221 (2): 286–9.
•Cnop M. et al.(2003).“Relationship of adiponectin to body fat
distribution, insulin sensitivity and plasma lipoproteins: evidence
for independent roles of age and sex”. Diabetologia. 46: 459–469.
•Hotta K. et al.(2001).“Circulating concentrations of the adipocyte
protein adiponectin are decreased in parallel with reduced insulin
sensitivity during the progression to type 2 diabetes in rhesus
monkeys”. Diabetes. 50:1126–1133.
REFERENCES
25. •Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF (2004)
T-cadherin is a receptor for hexameric and high-molecular-weight
forms of Acrp30/adiponectin.
•Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, et
al.(2007) Targeted disruption of AdipoR1 and AdipoR2 causes
abrogation of adiponectin binding and metabolic actions.
•Tsuchida A, Yamauchi T, Ito Y, Hada Y, Maki T, et al.(2004)
Insulin/Foxo1 pathway regulates expression levels of adiponectin
receptors and adiponectin sensitivity.
