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gene therapy of diabetes mellitus
1. GENE THERAPY OF DIABETES
MELLITUS
SANJU K
FIRST YEAR M.PHARM(PHARMACOLOGY)
2. Type 1 DM results from the
body's failure to produce
enough insulin. This form
was previously referred to as
"insulin-dependent diabetes
mellitus" (IDDM) or "juvenile
diabetes". The cause is
unknown.
Type 2 DM begins with insulin
resistance, a condition in
which cells fail to respond to
insulin properly. As the
disease progresses a lack of
insulin may also
develop.] This form was
previously referred to as "non
3. Genes susceptible for T1D
HLA-DQB1 HLA-DQB1 belongs to the HLA class II beta chain paralogues. This class II molecule
is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both
anchored in the membrane. It plays a central role in the immune system by
presenting peptides derived from extracellular proteins. Class II molecules are
expressed in antigen-presenting cells. the phenotype DQB1*0201/*0302 has a high
risk of late onset type 1 diabetes
INS The insulin gene (INS) on chromosome 11p15 encompasses 1430 base pairs (bp)
and results in the translation of preproinsulin. A variable number tandem repeat
(VNTR) region consisting of a 14 to 15 bp consensus sequence upstream of the INS
gene, in the INS promoter, is comprised of three classes of alleles: there is a higher
frequency of class I alleles with shorter repeat sequences in individuals with type 1
diabetes, whereas individuals with longer class III alleles are relatively protected
from type 1 diabetes. The VNTR regulates transcription rates of insulin and its
precursors.
CTLA4 cytotoxic T-lymphocyte antigen-4 gene (CTLA-4) encoded on chromosome
2q3CTLA-4 is a surface molecule found on activated T cells which produces a
negative signal by inhibiting the T cell receptor signaling complex ligand
interactions (blocks binding of CD80 and CD86). An A49G polymorphism in exon 1
4. Genes susceptible for T2D
PPARƳ Peroxisome proliferator-activated receptor-
Ƴ.one form of this gene(12pro) decreases
insulin sensitivity and increases T2D risk
ABCC8 ATP binding cassette, subfamily C, member
8)U. This gene encodes the high-affinity
sulfonylurea receptor (SUR1) subunit that is
coupled to the Kir6.2 subunit
8. Genes promoting islet
allograft/xenograft survival
• Anti apoptotic genes
• It mainly protects the beta cells from cytokine induced
destruction.
Eg: bcl-2,heme oxygenase-1,hsp70,dominant negative protein
kinase C delta,manganese superoxide dismutase
• Immuno regulatory genes
Eg: Indoleamine 2,3 dioxygenase
• Cytokines
Eg: IL-1 receptor antagonist protein
9.
10. For T2D
• All under clinical experimentation
• Mainly focuses on obesity related complications and
satiety centre
• Beta cell long with a beta cell growth factor
engineered to a vector could cure the disease
partially.
![Type 1 DM results from the
body's failure to produce
enough insulin. This form
was previously referred to as
"insulin-dependent diabetes
mellitus" (IDDM) or "juvenile
diabetes". The cause is
unknown.
Type 2 DM begins with insulin
resistance, a condition in
which cells fail to respond to
insulin properly. As the
disease progresses a lack of
insulin may also
develop.] This form was
previously referred to as "non](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)