Regulation of insulin levels Starter: what do each of the following cells produce and are they part of the endocrine or exocrine system; –α cells –β cells –Pancreatic cells surrounding tubules

Objectives Explain the role of the pancreas in blood glucose regulation Explain how insulin secretion is controlled by the β cells in the islets of Langerhans Compare and contrast the causes of type 1 and type 2 diabetes Discuss the use of insulin produced by genetically modified bacteria

Importance of Glucose Regulation Too little – Brain problems Too much –Osmotic water loss (cellular and systemic) –Damages blood vessels

We eat food containing carbohydrates

The carbohydrates are fully digested to glucose which is absorbed

The carbohydrates are fully digested to glucose which is absorbed

Role of the Pancreas 1.Digestion – secretes digestive enzymes 2.Metabolism Regulation Carbohydrates Lipids Proteins Produces primary messengers (hormones) Insulin Glucagon

Insulin discovered by Frederick Banting and Charles Best in Leonard Thompson (age 14, 65lbs) first patient successfully treated.

The pancreas detects the change in blood glucose concentration and releases the appropriate hormone

51 amino acids 2 chains linked by disulfide bonds 5800 Dalton molecular weight

Effects of Insulin Nearly all cells (80%) increase glucose uptake (seconds) –Active transport –Primarily affects liver and muscle –Brain tissue is excepted Alters phosphorylation of many key intracellular metabolic enzymes (minutes) Alters protein synthesis and gene transcription (hours)

Insulin Affects Tissues Differently Muscle –Uptake of glucose and immediate use (exercise) or storage as glycogen (Exercising muscles can take up glucose without insulin) Liver –Uptake of glucose and storage as glycogen Inhibits glycogen phosphorylase Activates glycogen synthase Inhibits glucose synthesis Promotes excess glucose conversion to fatty acids Adipose Tissue –Promotes glucose uptake and conversion to glycerol for fat production

Insulin and Fat Metabolism Liver cells store glycogen only up to 5-6% –Remaining glucose metabolized to fat –Triglycerides are synthesized and release into blood Adipose cells store fat –Inhibits breakdown of triglycerides –Stimulates uptake and use of glucose to form glycerol –Stimulates fatty acid uptake and conversion to triglycerides Lack of insulin –Free fatty acids build up in blood –Liver metabolizes to produce phospholipids and cholesterol –Can lead to excess acetoacetic acid production and buildup of acetone (acidosis, which can lead to blindness and coma)

Insulin and Protein Metabolism Promotes –Transport of amino acids –Protein synthesis –Gene transcription Inhibits protein degradation Prevents glucose synthesis in liver –Preserves amino acids Lack of insulin causes elimination of protein stores

Insulin Control Muscle  Glucose uptake  Glycogen synthesis Liver  Glucose uptake  Glycogen synthesis  Fatty acid synthesis  Glucose synthesis Brain No effect Pancreas Beta cells Gastrointestinal hormones Feedback  amino acids  glucose  triglycerides Adipose  Glucose uptake  Glycerol production  Triglyceride breakdown  Triglyceride synthesis  Insulin Most Cells  Protein synthesis Amino acids Blood glucose

Effects of Glucagon Prevents hypoglycemia –Powerful system to degrade glycogen –Increases glucose synthesis from amino acids Increases with exercise independent of blood glucose Exerts effects through cAMP second messenger system

Glucagon Control Liver  Glycogen breakdown  Glucose synthesis  Glucose release Brain No effect Pancreas Alpha cells Exercise Feedback Adipose  Triglyceride breakdown  Triglyceride storage  Blood glucose  Fatty acids Epinephrine (stress) Amino acids

Diabetes Mellitus Type I –Insulin dependent –Juvenile onset –Causes Increased blood glucose (300-1,200 mg/100ml) Increased blood fatty acids and cholesterol Protein depletion –Treated with insulin injections –Increases risk of heart disease and stroke –Can cause acidosis and coma

Diabetes Mellitus Type II –Non-insulin dependent –Results from insulin insensitivity –Elevated insulin levels –Associated with obesity –Can lead to insulin dependent form –Treated with weight loss, diet restriction, exercise and drugs

Diabetes 143 million suffer worldwide (W.H.O.) –Expected to double by 2025 –Costs $143B annually Treatment with insulin is not optimal –Does not mimic normal control system –Associated with serious health risks Direct transplantation has not proven feasible –Immunosuppression causes problems Use of semi permeable encapsulation may be possible –Must optimize for nutrient exchange but immune isolation –Biocompatible and structurally sound –Prevent allergic responses –Must provide glucose control Other options may be effective (e.g., gene therapy)

Diabetes mellitus Blood glucose level fluctuate due to eating and exercise Diabetes mellitus is a disease in which the body can no longer control the blood glucose levels This can lead to; –hyperglycaemia – blood sugar level too high –hypoglycaemia – blood sugar level too low

Types of diabets There are two main types of diabetes; –Type 1 – early onset –Type 2 – late onset

Type 1 diabetes Usually starts in childhood Aka insulin-dependant diabetes The body no longer makes any insulin Body cannot store excess glucose and glycogen It is thought that this is the result of an autoimmune response which the body destroys its own β cells

Type 2 Usually starts later in life due to obesity/aging Aka non-insulin dependant Body does not respond properly to insulin/ insulin is not produced enough Certain factors bring on earlier onset; –Obesity –Diet high in sugar –Being of Asian/ afro Caribbean –Family history

Insulin therapy Where does the insulin come from that is injected into people with type 1 diabetes?