1. Glycolysis
Gluconeogenesis

3. Pentose phosphate pathway

4. Glycogen metabolism

5. Blood Glucose

6. Blood Glucose Fasting blood glucose concentration (blood plasma)
(person who has not eaten in the past 3-4 hours)
3.9mmol/L – 6.1 mmol/L
70mg% – 110mg%
mean: 90mg%
It is tightly regulated as a part of metabolic homeostasis.

7. Blood Glucose Mean normal blood glucose levels in humans are about
90 mg/dl, equivalent to 5mmol/L.
Glucose levels rise after meals for an hour or two and are usually
lowest in the morning, before the first meal of the day.
Transported via the bloodstream from the intestines or liver to
body cells.
Failure to maintain blood glucose in the normal range leads to
conditions of persistently high (hyperglycemia) or low
(hypoglycemia) blood sugar.

8. Blood Glucose
If blood glucose levels fall below 3 mmol/L (hypoglycemia) this would lead to a loss of consciousness (coma).
If level goes above 10 mmol/L (hyperglycaemia) glucose will appear in the urine, the pH of the blood would fall and this also leads to coma.
If cells have inadequate amounts of glucose to catabolize, the cells immediately shift to the catabolism of fats for energy.
In starvation, proteins are also used for energy after carbohydrate and fats are depleted.

9. Maintaining Glucose Homeostasis
Goal is to maintain blood glucose levels between 70 and 110 mg%.
The levels of glucose in the blood are monitored by the cells in
the pancreas's Islets of Langerhans.
Two pancreas hormones play important roles in maintaining glucose homeostasis:
Insulin
Glucagon

10.  cells. (20%) secrete glucagon
 cells (75%) secrete insulin
 cells (5%) secrete somatostatin
A: Pancreatic islet with exocrine cells. B: Confocal image of an isolated islet immunolabelled for insulin (red), glucagon (green) somatostatin (blue).

11. Glucagan
If the blood glucose level falls to dangerous levels (as in very heavy exercise or lack of food for extended periods), the alpha cells of the pancreas release glucagon.
-- Convert glycogen into glucose (glycogenolysis).
-- Activates gluconeogenesis.
-- The glucose is released into the bloodstream, increasing blood sugar levels.
Glucagan

12. Proglucagon (158Aa) Glucagon (29Aa)

13. Insulin
When levels of blood sugar rise, the pancreas released a different hormone insulin, from beta cells.
-- Causes the liver to convert more glucose into glycogen (glycogenesis).
-- Activates glycolysis but inhibits gluconeogenesis.
-- Bind to insulin receptor and force body cells to take up glucose from
the blood through the glucose transporter.
-- Stimulates excess glucose to be converted into fat.
As a result, blood glucose levels drop.

14. Proinsulin Insulin

15. Mechanism of Insulin Action
The insulin receptor is a combination of 4 subunits held together by disulfide linkages: two -subunits lying outside the cell membrane and two -subunits protruding into the cell cytoplasm.

16. Mechanism of Insulin
When insulin binds to the -subunit in target tissues, the -subunits in turn become activated.

17. Mechanism of Action of Insulin
Activation of the -subunits triggers a series of reactions that draw the glucose transporter to the cell membrane or regulate metabolism of glucose.
Cells (liver, muscle, adipose) are now able to increase their uptake of glucose (w/in seconds after insulin binds with its membrane) .

18. Regulating Blood Glucose Levels
Blood glucose levels rise due to eating a carbohydrate containing meal
In response, the pancreas releases insulin into the blood to decrease glucose level.
After the meal is over and blood glucose level begins to fall to a low level:
The pancreas decreases insulin secretion
Glycogen synthesis in liver is stopped
Glucose uptake by cells from blood is prevented
If blood glucose levels continue to fall,
Glucagon will be released to increase the release of glucose from the cells.

19. Hyperglycemia
A condition in which an excessive amount of glucose circulates in the blood plasma (>10 mmol/L or 180 mg/dl),
Temporary hyperglycemia is often benign and asymptomatic.
Blood glucose levels can rise well above normal for short periods without producing any permanent effects or symptoms.
However, chronic hyperglycemia at levels more than slightly above normal can produce a very wide variety of serious complications over a period of years, including kidney damage, neurological damage, cardiovascular damage, damage to the retina etc.

20. Hyperglycemia
Exerts high osmotic pressure in extracellular fluid, causing cellular dehydration
Excess of glucose begins to be lost from the body in the urine: GLYCOSURIA

21. The following symptoms may be associated with acute or chronic hyperglycemia,
Polyphagia - frequent hunger, especially pronounced hunger
Polydipsia - frequent thirst, especially excessive thirst
Polyuria - frequent urination, especially excessive urination
Blurred vision
Fatigue
Weight loss
Poor wound healing (cuts, scrapes, etc.)
Dry mouth
Dry or itchy skin
Impotence (male)
Recurrent infections
Cardiac arrhythmia
Coma

22. Hypoglycemia Blood sugar less than 70mg% (3.9mmol/L) Symptoms include
shaking
sweating
nervousness
feeling irritable
blurry vision or headache
feeling tired
Coma

23. Diabetes mellitus
A condition in which the body either does not produce enough, or does not properly respond to insulin or both. This causes glucose to accumulate in the blood, often leading to various complications.
Mellitus– Latin for sweet as honey. In 1679, a physician tasted the urine of a person with diabetes and described as sweet like honey.
Diabetes– Greek for siphon or fountain for the characteristic frequent urination

24. Diabetes mellitus Symptoms: Hyperglycemia (high blood glucose)
Glucosuria (glucose in the urine)
Polyuria (frequent urination)
Polydipsia (drinking large amounts)
Polyphagia (frequent hunger)
Weight loss
Acids and ketones in the blood from lipid breakdown (toxic if high)
Coma if ketones build up
© 2008 Paul Billiet ODWS

25. Hyperglycemia > Glycosuria>Polyuria>Polydipsia
Excessive glucose in the kidney filtrate acts as an osmotic diuretic, inhibiting water reabsorption resulting in POLYURIA: huge urine output >>> decreased blood volume and dehydration.
Dehydration stimulates hypothalamic thirst centers, causing POLYDIPSIA: excessive thirst.

26. Polyphagia
POLYPHAGIA: excessive hunger and food consumption, a sign that the person is “starving in the land of plenty.” That is, although plenty of glucose is available, it cannot be used, and the cells begin to starve.
Without fuel, cells cannot produce energy >> fatigue and weight loss.
POLYURIA,
POLYDIPSIA,
POLYPHAGIA
= The 3 most important symptoms of diabetes
Poor with gold in home

27. Diabetes Mellitus Two main common forms: Type 1 diabetes Other names:
“Juvenile” diabetes
Insulin dependent diabetes mellitus (IDDM)
Type 2 diabetes
“Adult onset” diabetes
Noninsulin dependent diabetes mellitus (NIDDM)

28. Incidence of Diabetes Type 1 Diabetes 5-10 % of diabetics
Onset is generally before age 20
Average age of onset ~12
Type 2 Diabetes
90-95% of diabetics
Onset is generally after age 40

29. Type 1 Diabetes
Results from the body's failure to produce insulin. The majority of type 1 diabetes is of the immune-mediated nature.
Causes:
Immune-mediated destruction of ß cells
Genetic component
Immune system destroys beta cells of pancreas
May also be caused by a viral infection that damages the pancreas.
Pancreas is unable to make/secrete insulin.
Glucose cannot enter cells
Blood glucose levels rise
Glucose “spills” into the urine
Water moves into blood
Frequent need to urinate
Thirsty

30. Type 1 Diabetes
Cells use fats and proteins as an energy source, results in:
Weight loss
Ketones produced (due to “overuse” of fats for energy)  potential for diabetic acidosis
Fat  Fatty acids  Acetyl-CoA  Ketones:
acetoacetate; β-hydroxybutyrate; acetone
The increased ketones in the blood lower the pH of blood, resulting in a form of acidosis called KETOSIS, or ketoacidosis.
If too high, ketones are excreted in the urine: KETONURIA.

31. Type 1 Diabetes Treatment Insulin shots or pump
Highly regulate intake of carbohydrates
Consistent pattern of moderate carbohydrate intake to minimize fluctuations in blood glucose
Closely monitor blood glucose levels

32. Type 2 Diabetes
Results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with relative insulin deficiency.
Fewer insulin receptors on cells
More insulin is secreted to compensate
Eventually the islet cells cannot keep up with the demand
Less insulin binds to cells
Glucose enters cells SLOWLY
Hungry
Eat more
Blood glucose levels remain elevated
Glucose “spills” into the urine
Water moves into blood
Frequent need to urinate
Thirsty

33. Type 2 Diabetes Pancreas continues to make insulin
Often in large amounts to compensate for the insulin resistance of cells
May get to point where pancreas cannot keep up with the body’s needs and insulin is required.
Associated with obesity
As gain weight, cells make fewer insulin receptors
Insulin doesn’t bind as well to receptors

34. Type 2 Diabetes Recommendations Lose weight
Even moderate weight loss can help
Exercise
Increases number of insulin receptors
Improves binding of insulin to the receptors
Helps with weight loss

35. CAUSES OF TYPE-2 DIABETES
Two factors especially important in the development of type-2 diabetes:
1) Heredity: About a 5% risk of developing Type II diabetes if mother, father, or sibling has diabetes. Higher risk (up to 50%) if overweight.
2) Obesity: 80% of people w/ Type II diabetes are overweight when diagnosed and symptoms disappear in many of the obese patients when they lose weight.

36. Type I vs. Type II Diabetes
Type 1 (IDDM)
Type 2 (NIDDM)
Age at onset
Usually under 40
Usually over 40
Body weight
Thin
Usually overweight
Symptoms
Appear suddenly
Appear slowly
Insulin produced
None or littler
Relative deficiency
Insulin required
Must take insulin
May require insulin
Other names
Juvenile onset diabetes
Adult onset diabetes