Diabetes

Diabetes Homeostatc range of blood glucose = 70-110 mg of glucose/100 mL Usually there is more glucose in extracellular fuid than in cells Pancreas - Contains endocrine tssue (also has exocrine), but endocrine functons refer to insulin and glucagon hormones - Pancreatc islets aka. Islets of Langerhans. Tiny cell clusters that produce pancreatc hormone - Alpha cells – fewer, release glucagon - Beta cells – the majority, release insulin Islet Cells - Sense when each hormone is needed, release the hormones during the fed and fastng state appropriately - Independently involved in regulatng glucose levels (but both needed to regulate blood glucose levels) - Alpha cell = glucagon = hyperglycemic hormone = increases blood glucose - Beta cell = insulin = hypoglycemic hormone = decreases blood glucose - There are other islet cells that release small amounts of peptdes such as somatostatn (delta cells), pancreatc polypeptde (PP- by F cells), and others Glucagon Insulin - Made of 29 amino acids - Very potent (can cause a big reacton with very litle) - Target organ = liver - Directs events of the postabsorptve state, aka. The fastng state (when the GI tract is empty and body reserves are being broken down) - Energy is mainly coming from breakdown of glycogen and for skeletal muscle – FFA due to lipolysis Efects: - Increase blood glucose levels - Glycogenolysis: glycogen to glucose - Gluconeogenesis: synthesis of glucose from lactc acid and noncarbohydrate - Made of 51 amino acids - Consists of two aa chains linked by a disulfde bond - Synthesized as proinsulin frst (larger molecule) - Enzymes “clip” the middle porton of this proinsulin molecule producing insulin (occurs in the secretory vesicle just before it is released as insulin) - Directs events of the absorptve state, afer a meal. Glucose is being used as the main energy source Efects: - Most notceable just afer eatng - Decrease blood glucose levels - Also promotes protein synthesis (in muscle cells) and fat storage Downloaded by Kevin Lang (dilas34153@fesgrid.com) lOMoARcPSD|31076631

epinephrine, growth hormone, thyroxine, glucocortcoids Suppressors: - Somatostatn - SNS - Cortcosteroids Downloaded by Kevin Lang (dilas34153@fesgrid.com) lOMoARcPSD|31076631

- Causes anxiety, nervousness, tremors, weakness - Insufcient glucose to brain causes disorientaton, convulsions, unconsciousness, death - Usually caused by overdose of insulin, can be easily treated by ingestng sugar. Sometmes can be due to an islet tumor. Stress - Systems work to increase blood glucose levels - “stress hyperglycemia” - Observed both in traumatc stress and psychological Prediabetes: Both classifcatons are the grey area between normal glucose metabolism and the onset of diabetes. The signals to stmulate breakdown and release of glucose are stronger than the counterregulatory efects (glucagon, catecholamines, etc.) which create insulin resistance in the liver. (The liver stops listening to the hypoglycemic goal of insulin) 1) Impaired glucose tolerance 2) Impaired fastng glucose tolerance Type 1 Diabetes Mellitus: - Appears suddenly, usually before 15. Peaks at ages 2-6 and 10-14 - 10% of diabetc populaton - Caucasians are more susceptble - Immune system destroys beta cells, no insulin producton = glucose cannot enter cells - Liver keeps producing glucose, because body is getng a signal that glucose is not entering cells. Overproducton of glucagon also occurs. - Multgene immune disorder (genes have been localized on several chromosomes) - Viral infecton/toxic agent can trigger/onset the autoimmune process of the disease in people with a risk of diabetes Two forms of type 1: 1) 1A immune-mediated diabetes: most common - Polygenic type 1: 80-90%, afect two or more genetc loci (areas on specifc chromosomes) - Monogenic: rare and associated with IPEX syndrome - Latent autoimmune diabetes in adults (LADA): afer the age of 35, 2-12%, development of T-cell reactvity to islet antgens and autoantbodies to glutamic acid decarboxylase 65 (GADA65) - Genes of the major histocompatbility complex (MHC) are responsible - T-cells secrete cytokines (CD4) and cytotoxic cells (CD8) 2) 1B idiopathic: rare - Unknown how this onsets. Downloaded by Kevin Lang (dilas34153@fesgrid.com) lOMoARcPSD|31076631

a. It is the most common kind of diabetes b. Although genetc predispositon is strong, environmental factors do not contribute to its pathogenesis c Too much exercise and insulin could lead to diabetc ketoacidosis d Could be treated with sulfonylureas e Viruses, dietary factors, autoimmune destructon of the beta cell could be involved in its development Answer: e 2Which one of the following treatment combinatons is appropriate for the type of diabetes indicated: a. Type 2 (NIDDM): sulfonylurea, metformin, diet, exercise b. Type 2 (NIDDM): pancreas (or islet) transplantation and immunosuppression c. Type 1 (IDDM): strict dietary control and exercise with insulin only if necessary d. Type 1 (IDDM): a mixture of long-acting (ultralente) and intermediate-acting (NPH) three times a day before meals e. Type 2 (NIDDM): only treat high blood pressure, glycemia not as important Answer: a 3 Which one of the following statements is not true about insulin: a) it is normally made in the beta cells of the islets (of Langerhans) in the pancreas b) it circulates in the blood as a hexamer or a complex of 6 insulin molecules c) it is the result of the cleavage of a precursor molecule called proinsulin d) the rapid or ‘frst phase’ response of insulin to glucose is very important in its acton e) it binds to protein receptors in the target cell membranes Answer: b Downloaded by Kevin Lang (dilas34153@fesgrid.com) lOMoARcPSD|31076631