Diabetes mellitus type 1 is an autoimmune disease characterized by the destruction of pancreatic beta cells and an absolute deficiency of insulin. The normal process of glucose homeostasis and insulin metabolism is disrupted. Insulin is necessary to regulate glucose uptake and metabolism in the liver, skeletal muscle and other tissues. Without insulin, hyperglycemia develops. The pathogenesis of type 1 diabetes involves genetic susceptibility, autoimmune attack on beta cells, and environmental triggers that lead to beta cell destruction over time. The clinical signs include polyuria, polydipsia, and polyphagia with ketoacidosis a severe complication. Treatment requires lifelong administration of exogenous insulin through injections or pumps.

1. DiabetesmellitusTYPE1
DONEBY:
AbdulaleemAliQassemAlharfi

2. Glucose Homeostasis
The normal glucose homeostasis is tightly regulated by three
interrelated processes:
1.Glucose production in the liver.
2.Glucose uptake and utilization by peripheral tissue ,chiefly
skeletal muscle.
3.Action of insulin and counterregulatory hormones ,including
glucagon, on glucose uptake and metabolism.

4. Normal Insuline Metabolism
The major stimulus for both synthesis and release of insulin is
glucose.
The steps involved in biosynthesis ,release and action of insulin
areas follows:
1.Synthesis of insulin:
insulin is synthesized in the B−Cell of pancreatic
islets of Langerhans in the pancreas:
1.It is initially formed as a (pre −proinsulin)which is single chain
(86−amino acid) precursor polypeptide.
2.Subsequent proteolysis removes the amino terminal signal
peptide forming proinsulin.
(
3.Further cleavage of proinsulin gives rise to A ( 21−amino acids
and B (30−amino acids) chain of insulin, linked together by
connecting segment called C−Peptide, all of which are stored in the
secretory granules in the B−cells.
•
4.for therapeutic use,humen insulin is now produced by
recombinant DNA technology.

5. 2.Relgulation of insulin release:
Glucose is the key regulator of insulin secretion from B−Cells by
a series of steps:
1.Hypoglycaemia (glucose level below 70 or 80 mg̸dl)stimulates
transport into B−cells of a glucose transporter,GLUT2.
2.in islet transcription factor ,glucokinase ,causes glucose
phosphorylation.
3.metabolism of glucose to glucose−6−phosphate by glycolysis
generates ATP.
3.generation of ATP alters the ion channel activity on the
membrane .it causes inhibition of ATP−sensitive K channel on
the cell membrane and opening uo of calcium channel with
resultant influx of calcium, which stimulates insulin release.

6. 3.Action of insulin:
Half of insulin secreted from B−cells into portal vein is degraded
in the liver while the remaining half enters the systemic
circulation for action on the target cells:
1.Insulin from circulation binds to its receptor on the target
cells. This insulin this insulin receptor has intrinsic tyrosine
kinase activity.
2.This in turn ,activates post−receptor intracellular signaling
pathway molecules ,insulin receptor substrates(IRS )1 and 2
proteins.
3.This reaction on the target cell are responsible for the main
mitogenic and anabolic action of insulin ──glycogen synthesis
,glucose transport ,protein synthesis ,lipogenesis.
4.Besides the role of glucose in maintaing equilibrium of insulin
release, low insulin level in fasting state promotes hepatic
gluconeogenesis and glycogenolysis.

8. Diabetes mellitus DM
Is a group of metabolic disorders sharing the
common feature of hyperglycemia.
Hyperglycemia in diabetes results from defect in
insulin secretion ,insulin action or most commonly
,both.
:
Diabetes TYPE 1
Insulin−dependent diabetes mellitus (juvenile
diabetes):
is the autoimmune disease characterized by
pancreatic B cells destruction and an absolute
deficiency of insulin.

9. Etiology of DM type 1:
Primary : Immune mediated
Secondary: Idiopathic
most common precipitating factor is a failure to take insulin
:
,although other stressors such as
Unfavorable environmental factors
Hereditary predisposition
Intercurrent infection
Certain drugs
Trauma
Illness
Complication( Diabetes Ketoacidosis ,Coma)

10. Pathogenesis:
The main cause in DM type 1 is destraction of B─Cell mass, usually
leading to absolute insulin deficiency .
the pathogenesis for primary etiology is immune−mediated
currently is explained on the basis of 3 mutually−interlinked
mechanism :
Genetic susceptibility, autoimmune factors , certain environmental
factor.
Pathogenesis of type 1 DM can summed up by interlinking the
above three factors:
diabetes.
DR4 associated type1
−
1.Genetic
susceptibility:HLA−DR3,HLA
2.Destraction of B−cell mass occurs by autoimmune and takes
months to years,the clinical feature manifest after more than 80%
of B cell destroyed.
3.As in other autoimmune disease ,genetic susceptibility contribute
to only a part of diabetes risk ,and environmental factor must play
a role which specifically target B−Cells.

12. DIAGNOSIS
Clinical feature:
Sing and symptoms:
1.Polyuria frequent urination
Increased thirst
2.Polydipsia
3.polyphagia extreme hunger
When sever, diabetic ketoacidosis.

13. Pathologic feature:
:Microscopy
Reduction in number and size of
islets
Leukocyte infiltration in islet
(
(insulitis

14. TREATMENT:
TAKING INSULIN

15. THANK YOU