DIABETES TYPE II

1. DIABETES TYPE II ActoplusMet GROUP 1

2. Physiology of the Condition • a number of metabolic disorders with elevated blood glucose levels or Hyperglycemia. • These disorders usually result from defects in Insulin secretion, Insulin action, or both.

3. Physiology of the Condition • Type II usually manifests later in life, although now it is manifesting earlier on average • most common form of diabetes on a global scale; 95% of all diabetes cases. • MAJOR CONCERN: predicted that the global prevalence of diabetes will increase from about 194 million in 2003 to about 330 million by 2025.

4. Physiology of the Condition • A number of things can go wrong that keep cells from taking up glucose. • has been linked to hereditary factors (links to ethnicity). • Also strong correlation to environmental factors / lifestyles: namely obesity • Pima Indian Study: Arizona versus Mexico

5. Medical Consequences of No Treatment • Most of the complications from diabetes result from high levels of blood glucose. • Sugar builds up in the walls of blood vessels causing disruption and damage • long-term dysfunction and damage of organs, including the kidneys, eyes, nerves, heart, and blood vessels.

6. Medical Consequences of No Treatment • decreased peripheral blood flow and nerve damage lead to high rates of nontraumatic limb amputations. • Heart disease and stroke are also more prevalent in people with diabetes. The affected population is two to four times more likely to suffer heart disease. • With no treatment: DEATH

7. Insulin • Hormone released by beta cells of the pancreas • Allows glucose to enter the cell and be used for energy. • Glucose is absorbed directly into the blood, then insulin is secreted. • Insulin binds to plasma membrane receptors and is a signaling ligand for glucose transporters to open for glucose

8. Insulin • Insulin in the blood also inhibits the liver from releasing glucose into the blood stream when glucose is already present the blood. • 51 A.A. peptide, composed of two chains A and B, joined by disulphide bonds and arranged in a complex tertiary structure. • molecules aggregate in pairs (dimers) which then aggregate with Zinc to form hexamers, that comprise the Insulin granules in the pancreatic β cells.

9. Insulin

11. What Goes Wrong?

12. What Goes Wrong? • Somehow the cell can’t get the glucose. • impaired Insulin action (Insulin resistance) and/or impaired Insulin secretion • Unclear why or how the cells become insulin resistant: genetic and environmental factors (obesity, inactivity etc.)

13. What Goes Wrong? • Since cells can no longer accept the insulin signaling, either from insufficient or deformed insulin or faulty proteins involved in uptake or metabolism of glucose, the blood glucose levels rise, and the cells cannot get glucose to produce energy. • The cells signal they need glucose and the liver releases even more by breaking down glycogen and does not take up extra glucose. • Increased elevation of blood sugar!

15. What Can You Do? • The first suggestion is to EXERCISE and DIET • If these do not lower blood glucose levels then medication can be prescribed. • Several medications used for diabetes. • Actoplus Met is a combination of two types of drugs.

16. Actoplus Met • In 2005 Takeda Pharmaceuticals released Actoplus Met, as a combination drug to combat Diabetes Type II. • Comprised of metformin of the biguanide class that works on the liver and pioglitazone of the thiazolidinedione class that reduces insulin resistance. • The drug is distributed in tablet form as hydrochlorides.

17. Pioglitazone • Molecular Formula: C19H20N2O3S∙HCl • Molecular Weight: 392.90g/mol • Structural formula: • Relatively insoluble in water due to hydrocarbons. Carbonyl groups and amines can allow for H-bond interactions

18. Pioglitazone • Decreases insulin resistance in the body • Binds to perioxisome proliferator-activated receptors found in adipose, skeletal, and liver tissues involved in insulin action. • Pioglitazone is a synthetic ligand for these receptors which serve as transcription factors for genes that regulate cell metabolism.

19. Pioglitazone • Pioglitazone specifically targets PPAR gamma receptors, which increase glucose uptake decrease the release of glucose by the liver, increase glucose transporters 1 & 4, and decrease insulin resistance. • Believed to target genes of lipoprotein lipase, fatty acid transport protein, and acety Co-A synthase that metabolize fatty acids. • After cells have broken down their fatty acids they begin to require glucose and insulin resistance is improved and glucose can be imported.

20. Metformin • Molecular Formula: C4H11N5∙HCl • Molecular Weight: 165.62g/mol • Stuctural formula: • In the biguanide class because of double guanadine CN3 strucure. Amine groups make it very soluble in water

21. Metformin • Metformin from the French lilac has been used for centuries to combat symptoms of diabetes. • For many years the exact mechanism was unknown. • Lowers glucose production by the liver, decreases absorption of glucose from the GI tract, improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

22. Metformin • A 2001 study showed metformin may work by stimulating the AMP-activated protein kinase that monitors energy usage in cells. • When activated it inhibits energy requiring processes and activates energy producing pathways (catabolism of glucose!) by decreasing insulin resistance.

23. Costs • Diabetes is a costly disease for individuals and society because of its complications and because it is a lifelong condition. • The total health care costs of a person with diabetes in the U.S. is 2 to 3 times higher than one without. • Estimated that 16% of a hospital expenses were on people with diabetes.

24. Costs • Medicine taken is not only for maintenance of blood sugar, but medication may also be needed for chronic pain and various other conditions caused by the diabetes. • As the incidence rates of diabetes increases, so too will the costs of maintaining the disease. • Prevention is a way to combat increasing rates. Exercise and good diets are the key to prevention

25. Cost • Actoplus Met for example costs approximately $2.25 per tablet. • The pill must be taken ever day, essentially for the rest of your life. So from the average age of diagnosis, approximately 45, living another 30 years will cost approximately $25,000 on medication alone! • But, without these drugs the complications mentioned before will result.