Exploring the mechanisms underlying ‘’Type 2 diabetes’’ using Drosophila as a

study model

Mohd Saifullah Ansari M.Sc. (F) Genetics

Roll No. 15ZYM06 A.M.U.

DiabetesInsulin secretory dysfunctionInsulin resistance (muscles, fat, liver)Increased endogenous glucose productionDecreased incretin effectDeranged adipocytes biology

Insulin

A polypeptide hormone secreted by the β-cells of the pancreatic islets.

STANDARDMETAPHOR

INSULIN FUNCTION

HOMEOSTATIC FUNCTION

DiabetesResults from body’s

failure to produce insulin, and presently requires person to inject insulin

Results when pancreas does not produce enough insulin to control glucose

level or the cells not responding to insulin

Results when body of a pregnant women does not

secrete excess insulin required during

pregnancy leading to increased blood sugar

level

Pathogenesis of type 2 diabetes

Present scenario of diabetesWorldwide 415 million cases (2015); expected to be 642

million (2040)In India, 69.1 million cases in 201590% of cases are of type 2 DMIn 2015, one in 11 adults was affected; expected to be one

in 10 adults in 2040In every 10 sec. one person dies from diabetes5.0 million deaths in 2015

(www.idf.org)

Organisms being used as diabetic model

MODEL ORGANIS

MS

Keeshond Dog Biobreeding rat

NOD Mouse NZW Rabbit

D. melanogaster

Drosophila as a good model organism

SHORT LIFE SPAN

GENOME SEQUENCE

D

AVAILABILITY OF

MUTANTS

NO ETHICAL CONCER

N

HOMOLOGOUS FOR 70% HUMAN

DISEASE GENES

LARGE NO. OF

OFFSPRINGS

EASY TO MAINTAIN

AND MANIPULAT

E

Drosophila as a type 2 diabetic modelGlucose level in fruit fly is controlled by ILPs, GLPs

and AKH.IPCs in adult synthesize Ilp2 , Ilp3 and Ilp5.Drosophila fat body stores and mobilizes energy

reserves.Mutation of the Akh gene or gene encoding its

receptor (AkhR) , or the ablation of CC cells results in

severe obesity hypoglycemia lipid mobilization defects

Genetic pathways to glucose intolerance

Intrinsic regulators of ILPs output in Drosophila

Extrinsic regulators of ILPs output in Drosophila

Insulin resistance and feedback in Drosophila fat body cell

FUTURE DIRECTIONS

1. The development of new methods, such as for measuring hormones in metabolic studies of feeding, fasting and obesity in Drosophila.

2. The in vivo characterization of human diabetes susceptibility genes and their mechanisms of function.

3. Studies of the evolution and development of glucose-responsive insulin output.

Referenceswww.jax.orgwww.anim.med.kyotodmm.biologist.orgwww.biologist.orgwww.elvesier.co.inwikipedia