1. Physiology, Health & Exercise Lesson 18 z Normal BGL zPathology of diabetes mellitus (DM)

2. 2 Normal BGL & Diabetes Includes: zRole of insulin & glucagon zPancreas & changes in BGL zNon-insulin dependent diabetes mellitus (NIDDM) zInsulin dependent diabetes mellitus (IDDM)

3. 3 Normal Blood Glucose levels zGlucose- source of energy for body zCarbohydrates digested to glucose zAbsorbed by blood capillaries in villi zCarried to liver by hepatic portal vein zThen distributed to body cells

4. 4 Normal Blood Glucose levels If too much glucose (hyperglycaemia) in blood: zWhy does this happen? zHow does the body respond? zBGL monitored by receptors in Islets of Langerhans (pancreas)  Respond by stimulating an enzyme that promotes production of insulin (by  cells) zExcess glucose stored as glycogen by liver zBGL fall back to normal levels

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6. 6 Normal Blood Glucose levels If glucose levels in blood drop (hypoglycaemia): zWhy does this happen? zHow does the body respond? zBGL monitored by receptors in Islets of Langerhans (pancreas)  Respond by stimulating an enzyme that promotes production of glucagon (by  cells) zGlycogen converted into glucose by liver zBGL increase back to normal levels

7. 7 Normal Blood Glucose levels Example of homeostasis 1.What does this mean? 2.Why is it described as being negative feedback?

8. 8 Normal Blood Glucose levels Insulin can affect a number of different cell types, principally: zSkeletal muscle cells zLiver cells zFat cells

9. 9 Normal Blood Glucose levels zSkeletal muscle cells & fat cells have very low permeability to glucose in absence of insulin zInsulin acts by stimulating the uptake of glucose into muscle cells zLiver cells are quite permeable to glucose, so glucose enters whether or not insulin is present zBut insulin still increases uptake of glucose by liver cells & glycogen formation

10. 10 How does insulin act? zInsulin is a protein hormone zExtracellular hydrophilic 1.Binds to specific insulin receptors in cell membrane of target cell 2.Activated receptor promotes recruitment of glucose transporters from intracellular pool to cell membrane 3.glucose transporters increase insulin- mediated uptake of glucose into cell

11. 11 How does insulin act? 4.When insulin levels decrease, glucose transporters move from cell membrane to intracellular storage pool, where they can be recycled zUnder certain circumstances e.g. obesity, number of insulin receptors decreases zGlucose uptake by cell decreases zLeads to insulin resistance

12. 12 How does insulin act?

13. 13 Types of diabetes mellitus (DM) zTwo types: 1.Type 1- Failure of pancreas to produce adequate quantities of insulin  IDDM (insulin dependent DM) 2.Type 2-Failure of tissues to respond to insulin (insulin resistance)  NIDDM (non- insulin dependent DM)

14. 14 Type 1 or IDDM zAccounts for 5-10% of diabetes cases  Caused by destruction of some or all  - cells in Islets of Langerhans zInadequate insulin production zCommonly occurs in childhood zPreviously called early-onset or juvenile- onset diabetes

15. 15 Type 2 or NIDDM zMuch more common zAccounts for 90-95% of diabetes cases zPreviously called late-onset because more common in people over age of 40 zHowever becoming more common in younger people (and has been diagnosed in people as young as 13!) zMore than 80% of people with NIDDM are overweight zObesity is the greatest risk factor for NIDDM

16. 16 Type 2 or NIDDM cont… zCan produce insulin zHave insulin levels in blood normal or higher than normal zBut target cells (especially in liver & skeletal muscles) have become less sensitive to insulin zInsulin resistance zDeficiency of insulin receptors zCells less able to take up glucose zBGL rise

17. 17 Type 2 or NIDDM cont… zIn this case most people develop Insulin resistance before they develop diabetes zPancreas tries to compensate by producing more insulin  Eventually the  -cells become “worn out” zInsulin production decreases zCauses an increase in BGL