Mechanism of Diabetes Mellitus: and How Does It Affect Health Status

MECHANISM OF DIABETES MELLITUS
IN RELATION TO ANATOMY, PHYSIOLOGY, PATHOGENESIS,

PATHOPHYSIOLOGY AND MOLECULAR BIOLOGY
USING EVIDENCE-BASE INFORMATION
AND HOW DOES IT AFFECT HEALTH STATUS
Group 2
Advisor: Assoc. Prof. Ekachai Kovavisarach
Kittisak Sinphitukkul, Ph.D.
Chinnathan Chaisiri 6306300030
Nutthapong Iemsinworakul 6406300003
Chontipha Neeyakorn 6406300008
Pornmongkol Rattanasarun 6406300014
Somsiri Yoosuk 6406300018
Group Kunlapach Dechsengchuroj 6406300022
Pattheera Kongrid 6406300026
members Peerawit Engpongpan 6406300031
Somkiat Sarachat 6406300038
Patchara Polsongkhram 6406300044
Varitpol Charoenyingpaisal 6406300047
Thaksapond Eiamudomsuk 6406300052
Krongjit Sittikityotin 6406300053
AGENDA
01 Antomy Pathophysiology
Mechanism of DM Physiology Molecular biology
using evidence-based Pathogenesis
information
02
What Cause Diabetes
How does it Affect Health Status
MECHANISM OF DM IN RELATION TO ANATOMY
MACROVASCULAR MICROVASCULAR
COMPLICATIONS COMPLICATIONS
Diabetic retinopathy
The most common long-
term diabetes-related to
anatomy are:
Diabetic nephropathy
Diabetic neuropathy
MECHANISM OF DM IN RELATION TO ANATOMY
Teeth and Gums

Skin
Other parts of the body

Reproductive
can also be affected by system
DM
Immune system
Gastrointestinal
system
MECHANISM OF DM IN RELATION TO PHYSIOLOGY
Guyton and hall textbook of medical physiology 12th edition

Insulin receptor is a combination of four

subunits, 2 alpha subunits outside cell
membrane and 2 beta subunits that
penetrate through the membrane in
cytoplasm

The insulin binds with the alpha subunits

on the outside of the cell
beta subunits protruding into the cell

become autophosphorylated.
Autophosphorylation of the beta

subunits of the receptor activates a
local tyrosine kinase
Phosphorylation of multiple other

intracellular enzymes including a group
called insulin-receptor substrates
(IRS).that mediate the effects on glucose,
fat, and protein metabolism.
Effects on carbohydrate, fat, and

Guyton and hall textbook of medical physiology 12th edition protein metabolism.
EFFECT OF INSULIN ON CARBOHYDRATE
METABOLISM
Insulin Promotes Liver Uptake, Storage, and Use of Glucose
Insulin inactivates liver phosphorylase, enzyme that causes

liver glycogen to split into glucose.
Insulin increase the activity glucokinase, enzymes that

phosphorylation of glucose after it diffuses into the liver
cells, the glucose is temporarily trapped inside the liver cells
Insulin increases the activities of the glycogen synthase that

promote glycogen synthesis.
EFFECT OF INSULIN ON FAT METABOLISM
Insulin Promotes Fat Synthesis and Storage

Insulin increases the transport of glucose into the liver
cells. After the liver glycogen concentration reaches 5
to 6 percent, this in itself inhibits glycogen synthesis.
The glucose is first split to pyruvate in the glycolytic

pathway, and the pyruvate is converted to acetyl
coenzyme A, the substrate from which fatty acids are
synthesized.
EFFECT OF INSULIN ON FAT METABOLISM
Insulin Promotes Fat Synthesis and Storage
An excess of citrate and isocitrate ions in the citric
acid cycle have a direct effect in activating acetyl-
CoA carboxylase, the enzyme required to carboxylate
acetylCoA to form malonyl-CoA, the first stage of fatty
acid synthesis.
Insulin activates lipoprotein lipase in the adipose

tissue, which splits the triglycerides again into fatty
acids. absorbed into the adipose cells, where they are
again converted to triglycerides and stored.
EFFECT OF INSULIN ON PROTEIN METABOLISM AND
ON GROWTH
Insulin Promotes Proteins Synthesis and Storage
Insulin stimulates transport of many of the amino acids into the

cells.
Insulin increases the translation of mRNA, thus forming new

proteins. insulin “turns on” the ribosomal machinery. In the absence
of insulin, the ribosomes simply stop working, almost as if insulin
operates an “on-off ” mechanism.
Insulin also increases the rate of transcription

EFFECT OF INSULIN ON PROTEIN METABOLISM AND
ON GROWTH
Insulin Promotes Proteins Synthesis and Storage
Insulin inhibits the catabolism of proteins. Ability of

insulin to diminish the normal degradation of proteins
by the cellular lysosomes.
In the liver, insulin depresses the rate of

gluconeogenesis. It does this by decreasing the
activity of the enzymes that promote
gluconeogenesis.
PATHOGENESIS
PATHOGENESIS OF TYPE 1 DM
Destruction of Beta cells in
; Autoimmune process
pancreas
Insulin is absent or extremely low
Endocrine cells
Beta cells = insulin-producing cells
Insulin deficiency Alpha cells = glucagon-secreting cells
PATHOGENESIS OF TYPE 2 DM
Aging Medication
Genetic susceptibility Insulin resistance Unhealthy lifestyle
Initially, Beta cell of pancreas work

; blood glucose still normal
over time to increase insulin
Over many year, Insulin resistance Reasons why Beta cells “tire out”
worsens, Beta-cells “tire out” , Glucotoxicity
Deceased insulin secretion Lipotoxicity
Over many more years: Beta

cell deteriorate until they
finally stop producing insulin
PATHOPHYSIOLOGY (TYPE 1 DM)
GENE MUTATION DIET VIRUSES DRUGS/TOXINS STRESSES
(HLA GENE) (Milk/nitrosamines) (Rubella/Coxsakie) (Pentamidine/Vacor) (Repeated sickness)
Failure of maturing T- Mutation of HLA gene Molecular mimicry Damage Beta cells that T-
cells = Facilitate or prevent T-cell cells mistakenly
= Abnormal attack of receptor binding to Beta cells acknowledged as antigen.
Beta cells
Breakdown of self-tolerance of beta cells anti-insulin and anti-Gad65 in blood
High-blood glucose
Autoimmune attack on beta cells
in post-prandial
stage
PRE-
loss of beta cells to half the original
DIABETES Asymptomatic
less than 10 percent of functional beta cells TYPE 1 DM

https://calgaryguide.ucalgary.ca/pathogenesis-of-
diabetes-mellitus-dm-type-i/
PATHOPHYSIOLOGY (TYPE 1 DM)
https://www.osmosis.org/learn/Diabetes_mellitus
PATHOPHYSIOLOGY OF DIABETES MELLITUS TYPE 2
Beta-cell and Insulin resistance
increase Insulin-mediated decrease Insulin-mediated

glucose production at liver glucose uptake at skeletal muscle
decrease Insulin-mediated glucose

uptake at adipose tissue
Hyperglycemia
Diabetes Medicine Matters
MOLECULAR BIOLOGY
GLUT-4
Function :
Insulin-mediated glucose
uptake
Expression :
Predominantly in striated
muscle and adipose tissue
Stress responses
WHAT CAUSE OF DM
INSULIN RESISTANCE
Type 2 diabetes mainly results from insulin resistance. Insulin
resistance happens when cells in your muscles, fat, and liver don’t
respond as they should to insulin.
AUTOIMMUNE DISEASE
Type 1 diabetes and Latent autoimmune diabetes in adults (LADA)
happen when your immune system attacks the insulin-producing cells
in your pancreas.
HORMONAL IMBALANCES
During pregnancy, You may develop gestational diabetes if your
pancreas can’t produce enough insulin to overcome the insulin
resistance.
WHAT CAUSE OF DM
PANCREATIC DAMAGE
Physical damage to your pancreas from a condition, surgery or
injury can impact its ability to make insulin
GENETIC MUTATIONS
Certain genetic mutations can cause MODY and neonatal diabetes.
HOW DOES IT AFFECT
HEALTH STATUS
ACUTE DIABETES COMPLICATIONS
Hyperosmolar hyperglycemic state (HHS)
Diabetes-related ketoacidosis (DKA)
Severe low blood sugar (hypoglycemia)
LONG-TERM DIABETES COMPLICATIONS

Cardiovascular (heart and blood vessel) issues are the most
common type of long-term diabetes: they in clued
Coronary artery disease
Heart attack
Stroke
Atherosclerosis
HOW DOES IT AFFECT
HEALTH STATUS
LONG-TERM DIABETES COMPLICATIONS
Other diabetes complications include:
Nerve damage (neuropathy)
Nephropathy
Retinopathy
Diabetes-related foot conditions
Sexual dysfunction
Gastroparesis
THANK YOU
TO SEE THIS PRESENTATION
REFERENCES
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.116.022194
https://calgaryguide.ucalgary.ca/pathogenesis-of-diabetes-mellitus-dm-
type-i/
https://calgaryguide.ucalgary.ca/pathogenesis-of-diabetes-mellitus-dm-
type-ii/
https://www.mayoclinic.org/diseases-conditions/diabetes/symptoms-
causes/syc-20371444
https://my.clevelandclinic.org/health/diseases/7104-diabetes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258103/
https://www.osmosis.org/learn/Diabetes_mellitus

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MECHANISM OF DIABETES MELLITUS

IN RELATION TO ANATOMY, PHYSIOLOGY, PATHOGENESIS,

Teeth and Gums

Other parts of the body

Guyton and hall textbook of medical physiology 12th edition

Insulin receptor is a combination of four

Guyton and hall textbook of medical physiology 12th edition

The insulin binds with the alpha subunits

beta subunits protruding into the cell

Autophosphorylation of the beta

Phosphorylation of multiple other

Effects on carbohydrate, fat, and

Insulin inactivates liver phosphorylase, enzyme that causes

Insulin increase the activity glucokinase, enzymes that

Insulin increases the activities of the glycogen synthase that

Insulin Promotes Fat Synthesis and Storage

The glucose is first split to pyruvate in the glycolytic

Insulin activates lipoprotein lipase in the adipose

Insulin stimulates transport of many of the amino acids into the

Insulin increases the translation of mRNA, thus forming new

Insulin also increases the rate of transcription

Insulin inhibits the catabolism of proteins. Ability of

In the liver, insulin depresses the rate of

Insulin is absent or extremely low

Genetic susceptibility Insulin resistance Unhealthy lifestyle

Initially, Beta cell of pancreas work

Over many more years: Beta

Breakdown of self-tolerance of beta cells anti-insulin and anti-Gad65 in blood

less than 10 percent of functional beta cells TYPE 1 DM

increase Insulin-mediated decrease Insulin-mediated

decrease Insulin-mediated glucose

LONG-TERM DIABETES COMPLICATIONS

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