References

Endocrine PANCREAS
Physiology
EM Savoeun, MD
ICU Medical (KSFH)

Introduction
Four polypeptides secreted by the islets of Langerhans in
the pancreas
hormones insulin
hormones glucagon
polypeptide, somatostatin, plays a role in the regulation of
islet cell secretion
pancreatic polypeptide, is probably concerned primarily
with the regulation of HCO3 secretion to the intestine

Introduction
Insulin is anabolic, increasing the storage of glucose,
fatty acids, and amino acids.
Insulin excess causes hypoglycemia, which leads to
convulsions and coma.
Insulin deficiency, either absolute or relative, causes
diabetes mellitus

Glucagon is catabolic, mobilizing glucose, fatty acids,

and the amino acids from stores into the bloodstream.
Glucagon deficiency can cause hypoglycemia
Glucagon excess makes diabetes worse.
Excess pancreatic production of somatostatin causes
hyperglycemia and other manifestations of diabetes.
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termes
glycogenolysis: glycogen breakdown
increase the use of fats and excess amino
acids for energy production
gluconeogenesis: making new glucose
glycogenesis: glycogen production

Islet Cell Structure

Humans have at least four distinct cell types:
A, B, D, and F cells. A, B, and D cells are also
called , and cells
A cells secrete glucagon (20%)
B cells secrete insulin (6075%) -islets make up
about 2% of the volume of the gland
D cells secrete somatostatin
F cells secrete pancreatic polypeptide

Structure

Preprohormone:
Hormone insulin : 51 aminoacide
Deux chanes et
Deux ponts disulfures

Peptide C
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Glucose

Blood

Glut 2
Glucose Close of channel K+

Open of channel Ca++

Hexokinase
G6P
Depolarisation of membrane
-Cells

ATP
Insulin

Blood
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Properties of insulin and glucagon

Water soluble
Carried dissolved in plasma no special transport
proteins
Interact with cell surface receptors on target cells
Insulin and Glucagon
Insulin
Target tissues: liver,
adipose tissue, muscle,
and satiety center of
hypothalamus
Increases uptake of
glucose and amino acids
by cells

Glucagon
Target tissue is liver
Causes breakdown of
glycogen and fats for
energy

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Negative feedback regulation of

the secretion of glucagon (blue
arrows) and insulin (orange
arrows)

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Regulation of Glucagon and Insulin

Secretion
Factor

Insulin Glucagon

Nutrients:
- glucose 5mM
- glucose 5mM
- amino acids
- fatty acids

+
+
+

+
+
0

Hormones/neurotransmitters:
- GI tract (GPI...)
- Adrenaline
- noradrenaline

+
-

0
+
+
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Effects of islet cell hormones on the secretion

of other islet cell hormones

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Insulin and Insulinlike Activity in Blood

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Effects of Insulin

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Actions of insulin on adipose tissue; skeletal, cardiac, and

smooth muscle and the liver

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Glucose Transporters

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Why keep blood glucose concentration

constant?
Some tissues only metabolise glucose: CNS,
Red blood cells, kidney, eye
Metabolise glucose at constant rate
Rate of glucose uptake determined by blood
glucose concentration
Keep blood glucose concentration to enable
metabolism to proceed at constant rate.

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Processes affected by insulin and

glucagon
Process
Glucose uptake : muscle and
adipose tissue
Gluconeogenesis: liver
Glycogenesis: liver and
muscle
Glycogenolysis: liver

Insulin
+

Glucagon
0

+
-

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Processes affected by insulin and

glucagon
Process
Lipogenesis: liver and adipose
tissue
Lipolysis: adipose tissue
Ketogenesis: liver
Amino acid uptake: muscle
Protein synthesis

Insulin
+

Glucagon
-

+
+

+/+
0
0

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Additional metabolic problems due to

insulin deficiency
Muscle:
uptake of amino acids and protein synthesis ( proteolysis)
Adipose tissue:
esterification ( lipolysis)
Liver:
gluconeogenesis from muscle amino acids
ketogenesis from adipose tissue fatty acids
Consequences:
muscle wasting and weight loss
hyperglycaemia
ketosis

Disordered plasma glucose

homeostasis in insulin deficiency.
The heavy arrows indicate reactions that are
accentuated. The rectangles across arrows indicate
reactions that are blocked.
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Integrated control of blood glucose

concentration

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What happens to metabolism when insulin or

glucagon levels are abnormal?
Insulin
High hypoglycaemia
Low diabetes

Glucagon
High no significant effect
Low no significant effect

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Hypoglycaemia
Blood glucose < 3.0 mM
Uptake of glucose by glucosedependent tissues not adequate to
maintain tissue function.
CNS very sensitive:
Impaired vision, slurred speech,
staggered walk
Mood change aggressive
Confusion, coma, death

Stress response (release of

adrenaline):
Pale
Sweating - clammy

Plasma glucose levels at which various

effects of hypoglycemia appear
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Diabetes Mellitus
Group of metabolic diseases
Affect 3-4% of population in Cambodia
Characterised by:
chronic hyperglycaemia (prolonged elevation of blood
glucose)
leading to long-term clinical complications

Caused by:
Insulin deficiency failure to secret adequate amounts of
insulin from -cells

and/ or
Insulin resistance tissues become insensitive to insulin

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Classification of Diabetes
Two major types recognised clinically
Type 1 absolute insulin deficiency (loss of cells)
Type 2 relative insulin deficiency and/or insulin
resistance
Also Gestational Diabetes (only occurs during
pregnancy)

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Causes of hyperglycaemia
Insulin deficiency and/or insulin resistance affects:
Muscle:
uptake of glucose
glycogenesis

Adipose tissue:
uptake of glucose
lipogenesis and esterification

Liver
glycogenesis and glycolysis
gluconeogenesis
Oral glucose tolerance test
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Glucose tolerance testing

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Clinical consequences of
hyperglycaemia
Acute metabolic:
glycosuria (exceeds renal threshold)
polyuria (excess urine production)
polydipsia (thirst)

Chronic microvascular disease:

eye disease including retinopathy
kidney (nephropathy)
peripheral nervous system (neuropathy)

Chronic macrovascular disease:

coronary artery disease
stroke
poor peripheral circulation (feet)

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Effects of insulin deficiency

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Factors that stimulate and inhibit

insulin secretion

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Factors that stimulate and inhibit

glucagon secretion

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ADA Clinical Practice Recommendations

Diagnosis of Diabetes
A1C 6.5%
Test performed NGSP certified and standardized to DCCT*
FPG 126 mg/dl
No caloric intake for at least 8 hours*
2 hour glucose 200 mg/dl during an OGTT
Test performed as per WHO (75 g glucose)*
If classic symptoms of hyperglycemia = random glucose 200 mg/dl

NORMAL

PREDIABETES IFG or IGT

DIABETES

FPG < 100

FPG > 100 125 (IFG)

FPG > 126

2-h PG < 140

2-h PG 140 199 (IGT)

2-h PG > 200

A1c < 5.7%

A1c 5.7 6.4%

A1c > 6.5%

NGSP : National Glycohemoglobin Standardization Program

*In the absence of unequivocal hyperglycemia, criteria 1-3 should be confirmed by repeat testing
American Diabetes Association. Diabetes Care 323(Suppl 1), 2009

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Screening for and diagnosis of

GDM

DIABETES CARE, VOLUME 36, SUPPLEMENT 1, JANUARY 2013

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Pathogenesis of type 2 Diabetes

Diabetes

insulin Secretion

Normal glucose tolerance

1st phase
-10 -5

I.V. Glucose

2 nd phase

10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100

Duration (minutes)

Adapt de Weyer, et al. J Clin Invest. 1999; Ward, et al. Diabetes Care. 1984.

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Glucose

(mg/dL)

Natural History of Type 2 Diabetes

350

Post-meal glucose

300
250

Fasting glucose

200
150
100

Relative Function
( cell)

50
250

Insulin resistance

200
150
100

Insulin level

50

Incretin action

-15

-10

-5

Pre-diabetes
Onset
metabolic syndrome Diabetes

10

15

20

25

30

Years

Adapted from: UKPDS 33: Lancet 1998; 352, 837-853 ; DeFronzo RA. Diabetes. 37:667, 1988; Saltiel J. Diabetes. 45:1661-1669, 1996.
Robertson RP. Diabetes. 43:1085, 1994; Tokuyama Y. Diabetes 44:1447, 1995. Polonsky KS. N Engl J Med 1996;334:777.

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