This document summarizes different types of anti-diabetic agents used to treat diabetes mellitus. It describes insulin and how it is synthesized, stored and secreted in the body. It also discusses oral anti-diabetic agents including insulin secretagogues, biguanides, thiazolidinediones, and alpha-glucosidase inhibitors; and how each group works to lower blood glucose levels. Complications from insulin therapy and factors affecting insulin absorption are also summarized.

1. Anti-diabetic Agents Florencia D. Munsayac, MD, FPSECP, MBA, RMT

6. Diabetes – Insulin (synthesis, storage, secretion) This light micrograph of a section of the human pancreas shows one of the islets of Langerhans, center, a group of modified glandular cells. These cells secrete insulin, a hormone that helps the body metabolize sugars, fats, and starches. The blue and white lines in the islets of Langerhans are blood vessels that carry the insulin to the rest of the body.

7. Diabetes – Insulin (synthesis, storage, secretion) Insulin is a small protein consisting of an A chain of 21 amino acids linked by two disulfide (S—S) bridges to a B chain of 30 amino acids. Beta cells have channels in their plasma membrane that serve as glucose detectors. Beta cells secrete insulin in response to a rising level of circulating glucose .

9. Diabetes – Insulin (synthesis, storage, secretion)

14. Effects of Insulin on its Targets Transporters Tissues GlucoseKm (Mmo/L) Function GLUT 1 All tissues, esp.red cells, brain 1-2 Basal uptake of glucose; Transport across the BBB GLUT 2 B cells of pancreas; Liver; kidney; gut 15-20 Regulation of insulin release, other aspects of glucose homeostasis GLUT 3 Brain, kidney, placenta, other tissues < 1 Uptake into neurons, other tissues GLUT 4 Muscle, adipose 5 Insulin-mediated uptake of glucose GLUT 5 Gut, kidney 1-2 Absorption of fructose

25. Insulin Delivery Systems A. Portable Pen Injectors - to facilitate multiple SQ injections B. Continuous Subcutaneous Insulin Infusion Devices (CSII, Insulin Pumps) - encouraged for individuals who are unable to obtain target control while on multiple injection regimens & where excellent glycemic control is desired, such as during pregnancy - velosulin (reg. insulin) & insulin aspart and lispro C. Inhaled Insulin - have a rapid route and a relatively short duration of action - used to cover mealtime insulin requirements - to correct high glucose levels

26. Factors that Affect Insulin Absorption: - site of injection: abdomen, buttock, anterior thigh, or dorsal arm - type of insulin - subcutaneous blood flow: massage, hot baths, or exercise - smoking - regional muscular activity at the site of the injection - volume & concentration of injected insulin - depth of injection

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