Download glucagon

Hormonal Secretion of Pancreas 2
At the end of lecture students should be able to,
• Describe Endocrine pancreas,
• Describe Islet cells structure,
• Describe the Actions of glucagon
• Know the Factors affecting glucagon secretion,
• Describe the Glucagon action on cells.
•Describe the Insulin and glucagon regulate metabolism,
 Describe The regulation of blood glucose concentration,
• Describe What is Diabetes mellitus,
• Describe the Cardinal signs of DM,
• Describe the Paracrine regulation of somatostatin,insulin and
glucagon,
•Know the treatment of diabetes mellitus,
• Know the Clinical observation,
• Know the Rehydration and insulin management.
ENDOCRINE PANCREAS:
 Located behind the stomach between the spleen and
duodenum.
ISLET CELL STRUCTURE
 α cell : glucagon
 β cell : insulin
 δcell : somatostatin
δce
ll
α
cell
β
cell
GLUCAGON:
 Even in the absence of significant physical activity
or stress, several hours after carbohydrate intake,
blood glucose levels fall below 4.5 mM because of
utilization by brain and other tissues.
 Lowered blood glucose triggers secretion of
glucagon, a hormone produced by the  cells of the
islets of Langerhans.
 Glucagon increases blood glucose in several ways:
- stimulates breakdown of liver glycogen
- inhibits glucose breakdown in liver
- stimulates liver gluconeogenesis
 Together, these lead to accumulation of liver
glucose, allowing its export to blood.
 Glucagon stimulates fatty acid mobilization in
adipose tissue, liberating an alternate fuel for
tissues (other than brain).
GLUCAGON
Synthesis and secretion of
glucagon
ACTIONS OF GLUCAGON
Plasma: Glucose ↑
Amino acids ↓
Free fatty
acids↑
GLUCAGON
 A 29-amino-acid polypeptide hormone that is a potent
hyperglycemic agent.
 Produced by α cells in the pancreas
 Its major target is the liver, where it promotes:
 Glycogenolysis – the breakdown of glycogen to
glucose
 Gluconeogenesis – synthesis of glucose from lactic
acid and noncarbohydrates
 Release of glucose to the blood from liver cells.
GLUCAGON SIGNALING
SYNTHESIS
DNA in α cells
mRNA
Preproglucagon
proglucagon
glucagon
FACTORS AFFECTING GLUCAGON SECRETION:
GLUCAGON ACTION ON CELLS:
INSULIN & GLUCAGON REGULATE METABOLISM
THE REGULATION OF BLOOD GLUCOSE
CONCENTRATIONS
DIABETES MELLITUS (DM)
 A serious disorder of carbohydrate metabolism
 Results from hyposecretion or hypoactivity of insulin.
CARDINAL SIGNS OF DM
 The three cardinal signs of DM are:
 Polyuria – huge urine output.
 Polydipsia – excessive thirst.
 Polyphagia – excessive hunger and food consumption.
DIABETES MELLITUS TYPE I
 Type 1:
 beta cells destroyed- no insulin producedchronic
fasted state, "melting flesh", ketosis, acidosis,
glucosurea, diuresis & coma.
TYPE II A GROUP OF DISEASES:
 Insulin resistance keeps blood glucose too high
 Chronic complications: atherosclerosis, renal failure&
blindness.
SYMPTOMS OF DIABETES MELLITUS
PARACRINE REGULATION OF SOMATOSTATIN, INSULIN &
GLUCAGON
The well-fed state:
Stimulated by an
increase in blood
glucose level.
Insulin stimulates glucose consumption
and storage in muscle and liver.
Stored as glycogen
or triacyglycerol.24
 Excessive but incomplete oxidation of fatty acids in the
liver, resulting in overproduction of the ketone bodies
acetoacetate and -hydroxybutyrate. Acetoacetate can
convert to acetone, found in the blood of diabetics
(breath odor like ethanol).
 The overproduction of ketone bodies is called ketosis,
and their production is accompanied by decreased
blood pH, (acidosis) or ketoacidosis, potentially lifethreatening.
TREATMENT OF DIABETES
 Diet therapy
 2. Oral hypoglycemic agents
Insulin treatment.
4. Future treatment
 transplantation of islet cells
 artificial pancreas
 use of somatostatin
 Type 1 - insulin injections daily, or insulin infusion from
pump.
 Type 2 - do not usually require insulin treatment
because insulin synthesis partially preserved.
Treatment relies on diet and oral hypoglycemic agents.
DIABETIC KETOACIDOSIS
 Is the commonest cause of diabetes related death in
children.
 Most occur as a result of cerebral edema.
 Definition:
 Hyperglycosuria and ketonuria
 Hyperglycemia
 pH <7.3
 Bicarbonate < 15 mmol/L and > 5% or more
dehydrated
 +/_ vomiting
 +/_ drowsy
TREATMENT
 Confirm the diagnosis (HX, Biochem, And Clinical)
 Expansion of intravascular volume
 Correction of deficit in fluids, electrolytes, and acid base
status
 Initiation of insulin therapy to correct intermediary
metabolism
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CLINICAL OBSERVATION
MONITORING
Hourly- pulse rate, blood pressure, RR
Capillary, venous or arterial blood gases
Accurate I/O
Blood glucose, electrolytes, urea
Test urine for glucose and ketones
 Neurological Test –hourly or more frequently
ECG
 Diagnosis confirmed
REHYDRATION AND INSULIN MANAGEMENT
 FLUIDS
 Shock
 (poor peripheral pulses , reduced conscious level or
coma)
RESUSCITATION:
 Oxygen 100% by face mask
 Normal saline 0.9% 10ml/kg over 10-30 min until
circulation restored. May be repeated.
 NG tube, to drain stomach if vomiting or impaired
consciousness.
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