الفهرس 
Diabetes mellitusOnly 14 pages are availabe for public view
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Abstract
Diabetes mellitus Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects of insulin secretion and/or increased cellular resistance to insulin. Diabetes mellitus is classified into type 1, type 2, gestational and other specific types Manifested by polyuria, polydepsia and polyphagia. Diagnosed by FPG ≥126 mg/dl (7.0 mmol/l) = provisional diagnosis of diabetes. 2-h post load glucose ≥200 mg/dl = provisional diagnosis of diabetes. Symptoms of hyperglycemia and casual plasma glucose ≥ (200 mg/dL). Glycated hemoglobin (Hb A1C) ≥ 6.5%.
Screening is recommended to obese, hypertensive,family history of diabetes
or gestational diabetes and dyslipidemia.
Complications of diabetes include acute complications as DKA, HONK and
hypoglycemia. and chronic complications in form of microangiopathy as retinopathy, nephropathy and neuropathy. and macroangiopathy as coronary
heart disease strokes and peripheral arterial disease.
Treatment of diabetes includes:
1- Patient education about the disease nature and ideal food and
possible complications.
2- Diet patient should be educated about ideal food weight control.
3- Exercise has beneficial effects for diabetics and good glycemic
control.
4- Oral drugs include biguanides as metformin which is
recommended in all type 2 diabetics but has high incidence of
GIT complaint. And sulphonylureas which is potent drugs with
more incidence of hypoglycemia. Also TZDs which is good
option in treatment. And alpha glucosidase inhibitors but it is a
weak drugs can be combined with any other medications. With
new drugs GLP 1 analogue and DPP4 inhibitors which is
excellent drugs with high safety profile but expensive. Oral
drugs can be combined with insulin if oral drugs failed alone.
5- Insulin therapy which is the treatment of type 1 and some cases
of type 2 diabetes insulin has several preparations in market
with several treatment regimens for easy control of
hyperglycemia.
Apoptosis
Apoptosis is the process of Programmed cell death.
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The alternative to apoptotic cell death is necrosis, which is considered to be
a toxic process where the cell is a passive victim and follows an energyindependent
mode of death.
There is many differences between apoptosis and necrosis regarding
provoking stimuli, morphologic changes, inflammatory response, cell fate
and molecular changes.
Apoptosis activation occurs through caspases or caspase independent
Caspase activation occurs through 3 ways they are the death receptor
(extrinsic) and mitochondrial (intrinsic), and the third is an intrinsic pathway
involving the endoplasmic reticulum.
The caspases involved in apoptosis are subdivided into initiator caspases (2,
8, 9, 10) and effector caspases.
Apoptosis manifests in two major execution programs downstream of the
death signal: the caspase pathway and organelle dysfunction.
When caspases activated caspase cascade runs end with execution of the
cell.
Granzyme B: There is an accessory method of triggering apoptosis by the
serine protease granzyme B
Apoptosis is regulated by proapoptotic mediators which cause positive
induction and antiapoptotic mediators which cause negative induction
Regulators of mitochondrial apoptosis are Apoptosis-relevant proteins of the OMM are the VDAC and Bcl-2 members. The adenine nucleoside
translocator is situated in the IMM.
Activation of the pro-apoptotic molecule BAX appears to involve
subcellular translocation and dimerization.
The BH3-domain BIM also translocates to the mitochondria following
certain apoptotic stimuli.
the BH3-domain-only molecule BAD is phosphorylated on two serine sites.
Following TNFα or Fas treatment, BID, a BH3-domain-only molecule is
cleaved at its amino terminus.
Abnormalities in cell death regulation can be a significant
component of diseases such as cancer, autoimmune lymphoproliferative
syndrome, AIDS, ischemia, and neurodegenerative diseases such as
Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and
Amyotrophic Lateral Sclerosis. Some conditions feature insufficient
apoptosis whereas others feature excessive apoptosis.
potential methods of anti-apoptotic therapy includes stimulation of the IAP
(inhibitors of apoptosis proteins) family of proteins, caspase inhibition,
PARP (poly [ADP-ribose] polymerase) inhibition, stimulation of the
PKB/Akt (protein kinase B) pathway, and inhibition of Bcl-2 proteins. Apoptosis assays can be classified into Cytomorphological alterations,
DNA fragmentation, Detection of caspases, cleaved substrates, regulators
and inhibitors, Membrane alterations, Detection of apoptosis in whole
mounts and Mitochondrial assays.
Apoptosis & diabetes mellitus
Diabetes mellitus is one of the most common non-communicable diseases.
Pancreatic B-cell loss by apoptosis appears to play an important role in the
development of insulin deficiency and the onset and/or progression of the
disease.
β-Cell apoptosis is a key event contributing to the pathogenesis of type 1
diabetes mellitus.
induction of B-cell apoptosis by death receptors through studies in type 1
diabetes As a result, macrophages and cytotoxic T lymphocytes have been
accused of dealing the lethal blow to B-cells Studies from autopsies of
subjects affected by Type 2 diabetes demonstrated that in some, although not
all individuals with diabetes, there is a marked decrease in beta cells mass
free fatty acids, glucose, sulfonylurea, and the islet cell hormone termed
amylin can cause beta-cell apoptosis. This suggests that PCD may also be
involved in the pathogenesis of Type 2 diabetes.
New and convincing data indicating that increased apoptosis rather than
decreased neogenesis or replication may be the main mechanism leading to
reduced B-cell mass in type 2 diabetics. Cytokines, lipotoxity, and glucotoxity are three main stimuli for beta-cell
apoptosis.
Replication of somatic cells including B-cells occurs at a limited rate in
adulthood, B-cell apoptotic death is likely to occur at a slow rate, which is
compatible with the slow development of diabetes.
(GLP-1) has recently been found to have antiapoptotic properties. This new
property of GLP-1 has clinical relevance for the treatment of patients with
overt DM, possible prevention of DM during the stage of impaired glucose
tolerance.
In both animal models and in Type 2 diabetes patients Imatinib seems to
improve glycemic control, possibly via an insulin sensitizing effect.
B-cell death is a common event in MODY.
Renal apoptosis in diabetic nephropathy are scarce and scattered, but both
the intrinsic and extrinsic apoptotic pathway seems to be involved.
Diabetes causes apoptosis of neural and vascular cells in the retina.
Apoptosis plays an important role in the healing process, Apoptosis of
matrix-producing cells at this stage may interfere with the ability to produce
enough matrix and limit repair. Cardiomyocyte apoptosis causes a loss of contractile units which reduces
organ function and provokes cardiac remodeling which increase incidence of
heart failure.
New strategies to prevent B cell apoptosis include: (1) to remove stimuli
from the islet and keep it in a safety environment; (2) to attenuate the
apoptotic stimuli and stop the apoptosis at an early stage; (3) to block the
pathway of apoptosis and stop the process; (4) to change the balance
between pro and anti-apoptosis and reverse the cellular apoptotic process.