DIABETES MELLITUS

AND BLOOD GLUCOSE

REGULATION

Dr. ANUM KHAN KASI

Department Of Bio-chemistry
INSULIN
STRUCTURE
◼ Peptide Hormone
◼ Has 2 polypeptide
chains
• A chain (21 a.a)
• B chain (30 a.a)
▪ A and B chain
joined by two inter-
chain disulfide links
SYNTHESIS

▪ Produced by b cells in the Islets of Langerhans in the

pancreas

▪ Synthesized as a large precursor pre-proinsulin

by ribosomes attached to the endoplasmic reticulum.

▪ This initial preprohormone is then cleaved in the

endoplasmic reticulum to form a proinsulin

▪ Most of this is further cleaved in the Golgi apparatus to

form insulin and peptide fragments before being
packaged in the secretory granules.
INSULIN SECRETION
MECHANISM OF ACTION
▪ To initiate its effects on target cells, insulin first binds
with and activates a membrane receptor protein.

▪ The insulin receptor is a tetramer made up of two α-

subunits that lie outside the cell
membrane and two β-subunits
that penetrate the cell
membrane and protrude into
the cytoplasm.

▪ When insulin binds with the

alpha subunits on the outside of
the cell, portions of the beta
subunits protruding into the cell
become autophosphorylated.
▪ Thus, the insulin receptor is an example of an
enzyme-linked receptor.

▪ Autophosphorylation of the beta subunits of the

receptor activates a local tyrosine kinase, which in
turn causes phosphorylation of multiple other
intracellular enzymes including a group called
insulin-receptor substrates (IRS).

▪ The net effect is to activate some of these enzymes

while inactivating others.

▪ In this way, insulin directs the intracellular metabolic

machinery to produce the desired effects on
carbohydrate, fat, and protein metabolism.
EFFECTS OF INSULIN
STIMULATION OF INSULIN SECRETION
▪GLUCOSE
▪AMINO ACIDS
▪GIT HORMONES.

INHIBITION OF INSULIN SECRETION

▪SCARCITY OF DIETARY FUELS.
▪EPINEPHRINE (stress, trauma, extreme exercise).
GLUCAGON.
STRUCTURE
▪Poly Peptide Hormone
▪Chain of 29 amino acids
▪ Amino acid sequence of glucagon is the same in all
mammalian species
▪ Generally opposes the action of insulin.
Acts to maintain blood glucose levels by activation of
hepatic glycogenolysis and gluconeogenesis.
SYNTHESIS

▪ It is secreted by the alpha cells of the islets of

Langerhans when the blood glucose concentration
falls.
▪ Synthesized as a large precursor – preproglucagon

▪ Converted to glucagon through series of proteolytic

cleavages

▪ Half life is about 5 minute in the liver

▪ Inactivated in the liver

MECHANISM OF ACTION

▪ Most of the Actions of Glucagon Are Achieved by

Activation of Adenylyl Cyclase in hepatic cell membrane

▪ The binding of glucagon to hepatic receptors results in

activation of adenylyl cyclase and generation of the
second messenger cyclic AMP, which in turn activates
protein kinase, leading to phosphorylation that results
in the activation or deactivation of a number of
enzymes.
EFFECTS OF GLUCAGON
STIMULATION OF GLUCAGON SECRETION
▪Low blood glucose
▪Amino acids
▪Epinephrine

INHIBITION
▪Elevated blood glucose
▪Insulin.
 DIABETES MELLITUS

A heterogenous group of syndromes characterized by

an elevation of fasting blood glucose caused by a
relative or absolute deficiency in insulin.
 Risk Factor Defining Level
Abdominal obesity Waist circumference
Men: > 102cm or 40in
Women: > 88cm or 35in

High triglyceride levels > = 150 mg/dl

Low levels of High density Men: = < 40mg/dl

lipoprotein Women: = < 50mg/dl

High blood pressure > = 140/ > = 90mmHg

High fasting glucose levels > = 110mg/dl

 Diabetes Types

Type 1 Type 2
◼ Children/ Young onset ◼ Middle aged/ older
onset
◼ Acute onset ◼ Gradual
◼ Undernourished ◼ Often obese
◼ Weight loss ◼ Weight loss uncommon
◼ Ketosis ◼ Ketosis uncommon
◼ Insulin low or absent ◼ Insulin usually normal
or high
◼ Family history ◼ Family history common
uncommon
TYPE I
▪Characterized by absolute deficiency of insulin.
▪Type I diabetes is a result of autoimmune
destruction of beta cells, but it can also arise
from the loss of beta cells resulting from viral
infections, hereditary tendencies may play a role
as well.
▪ “Juvenile Diabetes”
▪Activated T lymphocytes infiltrate leading to
insulitis.
TYPE II
▪Type II diabetes is far more common than type I
diabetes(accounting for approximately 90% of all
cases of diabetes
▪This form of diabetes is characterized by impaired
ability of target tissues to respond to the metabolic
effects of insulin, which is referred to as insulin
resistance.
▪In contrast to type I diabetes, pancreatic beta cell
morphology is normal throughout much of the
disease, and there is an elevated rate of insulin
secretion. (Hyperinsulinemia)
DIAGNOSIS

▪ Urinary Glucose

▪ Fasting blood glucose - The fasting blood glucose level in

the early morning is normally 80 to 90 mg/100 ml;
above 110mgL100ml indicates diabetes

▪ Acetone breath – type I, Ketone bodies in urine – type

II

▪ HBA1c – Glycosylated Hb, N < 6%, > 8% - Poor control

▪ Insulin Levels - In type I diabetes, plasma insulin levels

are very low or undetectable during fasting and even
after a meal.
▪ In type II diabetes, plasma insulin concentration may be
several fold higher than normal and usually increases to
a greater extent after ingestion of a standard glucose
load.

▪ Glucose tolerance test- when a normal fasting person

ingests 1gm of glucose per kg of body weight, the blood
glucose levels rises from 90mg/100ml to 120 to
140mg/100ml and falls back to below normal in about 2
hours.
A diabetic patient, exhibit a much greater than normal
rise in blood glucose level, and the glucose level falls
back to the control value only after 4 to 6 hours
CLINICAL CONSEQUENCES.
Acute Chronic
▪Death ▪Death
▪Vascular Problems
▪Diabetic Ketoacidosis
▪IHD
▪Hyperosmolar non
ketotic state ▪Retinopathy- blindness

▪Hypoglycaemia ▪Nephropathy – end

stage renal disease
▪Neuropathy
▪Amputation
▪Weight loss
▪Diabetic ulceration
DIABETES TREATMENTS

▪Type 1 has absolute requirement for insulin.

▪In persons with type II diabetes, dieting and
exercise are usually recommended in an attempt to
induce weight loss and to reverse the insulin
resistance.
If this fails, drugs may be administered to increase
insulin sensitivity or to stimulate increased
production of insulin by the pancreas.
In many persons, however, exogenous insulin must
be used to regulate blood glucose.
THANK YOU.