The document summarizes the regulation of blood glucose levels. It discusses how glucose levels are maintained within a narrow range through negative feedback involving the pancreas and hormones like insulin and glucagon. Insulin regulates glucose by promoting its uptake in tissues and storage, while glucagon stimulates glucose production when levels fall. Glucose comes from digestion, liver glycogen stores, and gluconeogenesis. Factors that increase or decrease blood glucose levels are also outlined.

1. Regulation of Blood Glucose
presented by
Abdulrahman H. Amer
P.S.Medical College
Sardar Patel University
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2.  The maintenance of glucose level in blood
within narrow limits is a very finely and
efficiently regulated system.
 This is important , because it is essential to
have continuous supply of glucose to the
brain.
 Brain has an obligatory requirement for
glucose.
 RBC and renal medulla are also dependent on
glucose of meeting their fuel needs.
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3. Blood sugar levels are regulated by negative feedback in
order to keep the body in homeostasis.
The levels of glucose in the blood are regulated by the
cells Islets of Langerhans of pancreas.
Normal Blood Glucose
Random blood sugar : 70 to 140 mg/dl
Fasting state : 70 to 110 mg/dl
Postprandial : up to 140 mg/dl
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4.  Glucose is derived from 3 sources
1) Intestinal absorption of dietary carbohydrates
2) Glycogen breakdown in liver and kidney.
 Liver stores 25-138 grams of glycogen, a 3 to 8 hour
supply.
3) Gluconeogenesis, the formation of glucose from
non-carbohydrate precursors .
 These include lactate and pyruvate, amino acids
(alanine and glutamine).
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5.  The plasma glucose level at an instant depends
on the balance between glucose entering and
leaving the extracellular fluid.
The major factors which cause entry of glucose
into blood are
 Absorption from intestines
 Glycogenolysis(breakdown of glycogen)
 Gluconeogenesis
 Hyperglycemic hormones (glucagon, steroids)
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6. Factors leading to depletion of glucose in the
blood :
 Utilization by tissues for energy.
 Glycogen synthesis
 Conversion of glucose into fat (lipogenesis)
 Hypoglycaemia hormone ( insulin).
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7.  A steady maintenance of blood glucose with in
a narrow range
 Fasting state and fed states – their effects on
blood glucose (BG )
 Rate of glucose appearance Ra
 Rate of glucose disappearance Rd must be in
balance
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9.  When we eat food, our blood glucose
concentration increase , which stimulates insulin
secretion from -cells and final glucose
absorption by peripheral tissues.
 In between meals or in times of starvation, we are
not taking in glucose and, therefore, experience a
drop in blood glucose.
 During these times, the -cells release glucagon,
which stimulates the liver to make glucose by
glycogenolysis and gluconeogenesis, and thereby
increase blood glucose to normal levels.
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12. Glucose in balance
High blood glucose triggers the pancreas to release insulin.
Pancreas releases
insulin
Blood vessels carry insulin
and glucose to cells

13. Glucose in balance
Low blood glucose triggers the pancreas to release glucagon
Pancreas releases
glucagon
Blood vessels carry glucagon
to the body to trigger the
release of stored glucose
back into the blood.

14. Glucose in balance
The ability of the body to maintain balance and
regulate internal conditions is called homeostasis.
Balanced
Blood Glucose

15.  Short fast
◦ Utilizes free glucose (15-20%)
◦ Break down of glycogen (75%)
 Overnight fast
◦ Glycogen breakdown (75%)
◦ Gluconeogenesis (25%)
 Prolonged fast
◦ less of liver glycogen remains.
◦ Gluconeogenesis becomes only source of
glucose
◦ Muscle protein is degraded for amino acids.
◦ Lipolysis generates ketones for additional fuel.
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16. Pancreas:
One of the major players in glucose
homeostasis, the pancreas releases the hormones,
insulin and glucagon, that control blood glucose.
Liver:
This organ takes up glucose when levels are high
and releases glucose when levels are low. It
stores glucose as glycogen. It is key for glucose
regulation.
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17. Muscles:
Our muscles are able to take up and store lots of
glucose when insulin is present.
`Fat cells :
take up glucose when insulin is present.
Brain:
The brain takes up glucose whenever it needs
energy, and doesn’t require insulin.
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19. In the post prandial state (after a meal)
 Remember there are two separate signaling events
 First signal is from the ↑ Blood Glucose to pancreas
 To stimulates insulin secretion in to the blood stream
 The second signal from insulin to the target cells
 Insulin signals to the muscle, adipose tissue and liver to
permit to glucose in and to utilize glucose
 This effectively lowers Blood Glucose
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20. Hormones from pancreas:
 Insulin
 Somatostatin
 Glucagon
 Amylin
Hormones from adrenal glands:
Adrenal medulla adrenal cortex
Epinephrine Cortisol
Hormones from anterior pituitary gland:
 Adrenocorticotropic Hormone (ACTH)
 Growth Hormone (GH)
Hormone From Thyroid Gland:
Thyroxine
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21. Insulin is a peptide hormone produced by beta cells in the pancreas .
 It regulates the metabolism of carbohydrates and fats by promoting the
absorption of glucose from the blood to skeletal muscles and fat tissue and
by causing fat to be stored rather than used for energy.
Tissue of Origin Pancreatic β cells
Metabolic Effect
 Enhances entry of glucose into cells.
 Enhances storage of glucose as glycogen, or conversion to fatty acids.
 Enhances synthesis of fatty acids , proteins and nucleic acids.
 Suppresses breakdown of proteins into amino acids, of adipose tissue into
free fatty acids.
Effect on Blood Glucose- decrease .
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22.  Insulin is protein hormone with 2 polypeptide
chains, A chain and B chain .
 The A chain has 21 amino acids and B chain has
30 amino acids , both are joined by inter chain
disulphide bonds .
 –Synthesized from pro-insulin
 ––Anabolic hormone
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A Chain
Insulin
MW 5808
B Chain
C Chain

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25. •Beta Cells make and secrete
Pre-pro-insulin
cleaved
Pro-insulin
cleaved
Insulin C-peptide
Measures endogenous insulin secretion when
exogenously administered insulin interferes with
measurement
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26. 1- glucose : Glucose induced Insulin secretion
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 Glucose enters the beta cells
through uniporter GLUT 2
 Oxidative phosphorylation
 ATP closes the ATP gated K+
channel and depolarizes the cell
membrane
 Depolarization opens the voltage
gated Ca+ channels
 Ca+ enters the beta cells
 This leads to exocytosis of
Insulin and secretion

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28.  Insulin is rapidly degraded by the liver .
 Plasma half –life is less than 5 minutes.
 An insulin specific protease (insulinase) is
involved in the degradation of insulin .
 50% of degradation in liver
 50% of degradation in other target tissues and
kidney
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29. Cell-surface receptors:
α subunits contain
insulin binding sites
plasma membrane
β subunits have tyrosine
Kinase activity
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30. Insulin binding to α subunit
regulates β subunit activity.
Auto-phosphorylation of β subunit
⇑ tyrosine kinase activity
phosphorylation of other substrates
activation of phospho-inositide3-kinase
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31. 1- Insulin receptors :
Insulin act by binding to plasma membrane receptor
on the target cells.
In obesity the number of receptors are decreased
and target tissue becomes less sensitive to insulin
( DM type 2).
 Insulin Receptor is a tyrosine kinase.
 Insulin Receptor phosphorylates intracellular
signaling molecules.
 Stimulates insertion of GLUT-4 proteins which
let in glucose.
 Stimulate glycogen, fat and protein synthesis.
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33. 2- signal transduction
Insulin binds to the alpha subunit
This binding activates the tyrosine kinase activity
of beta subunit , leading to autophosphorylation of
beta subunit.
This event , in turn , phosphorylates insulin
receptor substrates.
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34. 3- gene- transcription (new enzyme synthesis)
Insulin act at the transcription level to regulate
synthesis of more than 100 proteins .
A- insulin induces the following enzymes:
- glucokinase
- pyruvate kinase
- phospho fructo kinase
- acetyl CoA carboxylase
B- insulin represses the following enzymes
 Glucose -6- phosphatase
 Phosphoenol pyruvate carboxykinase
 Fructose 1,6- bisphosphatase
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35. 4- DNA synthesis :
Through the IRS-1 pathway, insulin increases
DNA synthesis, cell growth and anabolism.
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36. 36
Activated IRTK
PO
PO
OP
OP
Extracellular
Cytoplasm
Glucose
Glucose transport
(muscle/adipose)
Activation of protein
phosphatase
NUCLEUS
Cell growth
and replication
DNA synthesis
(protein phosphorylation)
Signal transduction
(e.g., phosphorylation of IRS)
metabolic
responses
GLUT-4
mitogenic
response
mRNA synthesis
Protein
synthesis

37. 5- glucose uptake :
Insulin increases the activity of Glu T4 in cells.
Glucose Entry in to the Cell
 Insulin/GLUT4 is not the only pathway
 Insulin-dependent, GLUT 4 - mediated
◦ Cellular uptake of glucose into muscle and adipose tissue
(40%)
 Insulin-independent glucose disposal (60%)
◦ GLUT 1 – 3 in the Brain, Placenta, Kidney
◦ SGLT 1 and 2 (sodium glucose symporter)
◦ Intestinal epithelium, Kidney
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38.  insulin Secreted into portal circulation
Approximately 50 units of insulin is secreted per
day.
 Normal insulin level in blood is 5-15
microunits/ml.
 Insulin and c- peptide are synthesized and
secreted in equimolar quantities. Therefore ,
measurement of c- peptide is an index of rate
of secretion of insulin.
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39. Insulin plays central role in
regulation of the metabolism
of carbohydrates , lipids and
proteins .
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40. •Insulin lowers blood glucose
Increase uptake of glucose most tissues
especially muscle and fat by increasing
transporters (GLUT 4)
Inhibits hepatic glucose production .
Consequences of Insulin Deficiency
Hyperglycemia  osmotic diuresis and
dehydration
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41. Increases Amino Acid uptake by muscle.
•Increases protein synthesis and decreases
protein breakdown.
Consequences of Insulin Deficiency
Muscle wasting
If absolutly insulin deficient--- skeletal muscle
wasting
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42. Insulin increases:
1. Glucose uptake by fat cells
2. Triglyceride uptake by fat cells (increase
endothelium capillary bound lipoprotein lipases–
clears fat from the blood)
3. Lipogenesis (triglyceride synthesis)
Insulin decreases:
Triglyceride breakdown in adipose tissue by
decreasing the activity of hormone sensitive lipase.
Consequences of Insulin Deficiency
Elevated FFA levels
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43.  Inhibits ketogenesis
 Ketogenesis: is the process by which ketone
bodies are produced as a result of fatty acid
breakdown.
 Consequences of Insulin Deficiency
Ketoacidosis
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44. Glucose is taken up and broken down to make
ATP
Excess ATP is present and therefore activity of
Na+/K+ ATPase is enhanced
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45. Stimulates Inhibits
 ‹Liver glycogen synthesis glycogenolysis
triglyceride synthesis ketogenesis
gluconeogenesis‹
 Skeletal Muscle
glucose uptake
protein synthesis protein degradation
glycogen synthesis glycogenolysis
 ‹Adipose tissue
glucose uptake
triglyceride storage lipolysis
Inhibits catabolic
processes
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46. Glucagon is polypeptide hormone with 29 amino acids .
 It is secreted by the alpha cells of pancrease in response
to hypoglycaemia .
 Glucagon has half- life in plasma at about 4-6 minutes.
 It is inactiveated in the liver.
Entero-glucagon is peptide hormone secreted by duodenal
mucosa, having same immunological and physiological
properties of glucagon.
 The major regulator of secretion of glucagon is glucose.
 Increase blood glucose level inhibits secretion of
glucagon.
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47.  Glucagon is most potent hyperglycaemic
hormone
 It is anti insulin in nature.
 Glucagon stimulates glycogenolysis and
gluconeogenesis in liver but not in muscle .
 In glycogenolysis,the active form of glycogen
phosphorylase is formed under the influence
of glucagon.
It depresses glycogen synthesis .
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48.  Glucagon increases plasma free fatty acid
level
 In adipose tissue glucagon favors beta-
oxidation, as it activates carnitine acyl
transferase .
 Ketogenesis is favored .
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ACTION OF GLUCAGON

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52. Somatostatin :(also known as growth hormone-inhibiting
hormone (GHIH)
- It is a peptide hormone that regulates the endocrine system and
affects neurotransmission and cell proliferation via interaction
with G protein-coupled somatostatin receptors .
 Inhibition of the release of numerous secondary hormones.
 Somatostatin inhibits insulin and glucagon secretion.
Tissue of Origin
Pancreatic δ Cells
Metabolic Effect
Suppresses glucagon release from α cells (acts locally).
Suppresses release of Insulin, Pituitary tropic hormones, gastrin
and secretin.
Effect on Blood Glucose- decrease
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53.  The second early response hyperglycemic hormone.
 This effect is mediated through the hypothalamus in
response to low blood glucose
 Stimulation of sympathetic neurons causes release of
epinephrine from adrenal medulla .
 Epinephrine causes glycogen breakdown,
gluconeogenesis, and glucose release from the liver.
 It also stimulates glycolysis in muscle
 Lipolysis in adipose tissue,
 Decreases insulin secretion and
 Increases glucagon secretion.
 Effect on Blood Glucose- increase
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54.  Tissue of Origin
 Adrenal cortex
 These are long term hyperglycemic hormones
Activation takes hours. to days.
◦ Cortisol and GH act to decrease glucose utilization
in most cells of the body
◦ Effects of these hormones are mediated through the
CNS.
 Metabolic Effect
 Enhances Gluconeogenesis
 Antagonizes Insulin.
 Effect on Blood Glucose- increase
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55.  Tissue of Origin
 Anterior pituitary
 Metabolic Effect
 Enhances release of cortisol.
 Enhances release of fatty acids from adipose tissue.
 Effect on Blood Glucose- increase
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56.  Tissue of Origin
 Anterior pituitary
 GH increased cause insulin resistance.
 Metabolic Effect
 Antagonizes Insulin
 Effect on Blood Glucose- increase
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57. Reduction in the blood glucose level also
promotes secretion of ACTH and the growth
hormone from the pituitary gland through the
hypothalamus.
ACTH acts on the adrenal cortex to promote
glucocorticoid secretion (cortisol in humans).
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58.  Tissue of Origin
 Thyroid
 Metabolic Effect
 Enhances release of glucose from glycogen;
 Enhances absorption of sugars from intestine
 Effect on Blood Glucose- increase
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59.  Secreted by pancreatic beta-cells
 An anorectic hormone
 Works on the brain to stimulate the feeling of satiety.
 This results in decreased gastric motility,
 decrease carbohydrate absorption,
 and decreased appetite.
B cell damage also have amylin deficiency so may feel
hungry more.
Effect on Blood Glucose- decrease
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60. 2- Gastrointestinal hormones:
insulin secretion is enhanced by secretin ,
pancreozymin, and gastrin . After taking food ,
these hormones are increased .
3- Proteins and amino acids: leucine and arginine
are stimulants.
4- Parasympathetic and beta –adrenergic
stimulation
5- Glucagon and growth hormone .
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62. Thank you
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