Group 3 Concepcion Contacto Cordero Cornejo Cornell Cortez Cruz

65 y.o semi retired college professor Type 2 diabetes 4 years ago TREATMENT
1x a day sulfonylurea 2x a day insulin injection Weight loss Regular exercise

2 years ago:
+ gallstones (removed by surgery)

After a week:
Increase insulin dosage

It is composed of the following parts: 1. Head 2. Uncinate process 3. Neck 4. Body 5. Tail

The part of the pancreas with endocrine function is made up of approximately a million cell clusters called islets of Langerhans. Four main cell types exist in the islets. They are relatively difficult to distinguish using standard staining techniques, but they can be classified by their secretion:

 1. 2. 3. 1. 2. 3.

Main cell types: cells-secrete glucagon (increase glucose in blood) cells secrete insulin (decrease glucose in blood) delta cells secrete somatostatin (regulates/stops and cells) Minor cell types: PP cells- secrete pancreatic polypeptide D1 cells- secrete vasoactive intestinal polypeptide G cells- secrete gastrin

- is a small protein, with a molecular weight of about 6000 Daltons. -It is composed of two chains held together by disulfide bonds with the A chain and the larger B chain -is synthesized in significant quantities only in beta cells in the pancreas

Beta cells in the pancreas Preproinsulin-translated single chain insulin mRNA Proinsulin- removal of preproinsulin signal peptide during insertion into the endoplasmic reticulum -is exposed to several specific endopeptidases which excise the C peptide, thereby generating the mature form of insulin. Insulin and free C peptide -are packaged in the Golgi into secretory granules which accumulate in the cytoplasm.

Insulin secretion in beta cells is triggered by rising blood glucose levels. Starting with the uptake of glucose by the GLUT2 transporter, the glycolytic phosphorylation of glucose causes a rise in the ATP:ADP ratio. This rise inactivates the potassium channel that depolarizes the membrane, causing the calcium channel to open up allowing calcium ions to flow inward. The ensuing rise in levels of calcium leads to the exocytotic release of insulin from their storage granule

Insulin secretion in beta cells is triggered by rising blood glucose levels. Starting with the uptake of glucose by the GLUT2 transporter, the glycolytic phosphorylation of glucose causes a rise in the ATP:ADP ratio. This rise inactivates the potassium channel that depolarizes the membrane, causing the calcium channel to open up allowing calcium ions to flow inward. The ensuing rise in levels of calcium leads to the exocytotic release of insulin from their storage granule

Increase Insulin Secretion Decrease Insulin Secretion Increased blood glucose Decreased blood glucose Increased blood free fatty acids Fasting Increased blood amino acids Somatostatin Gastrointestinal hormones a-Adrenergic activity (gastrin, cholecystokinin, secreting gastric inhibitory peptide) Glucagon, growth hormone, cortisol Parasympathetic stimulation; acetylcholine b-Adrenergic stimulation Sulfonylurea drugs (glyburide, tolbutamide)

-secreted by the alpha cells of the islets of the langerhans when the blood glucose concentration falls -increased blood glucose concentration,an effect exactly opposite that of insulin Effects: 1.Breakdown of liver glycogen(glycogenolysis) 2. Increased gluconeogenesis in the liver

Production: B-cells f Pancreas Physiological Action:

Decrease Blood glucose levels by inhibiting release

of glucagons Regulation of CHO and Fat metabolism. Cause cells in the Liver, Skeletal Muscle and Fat tissues to take up Glucose in the blood.
Storage form:
Liver & Skeletal Muscle Glycogen Adipocytes Triglyceride

Control of cellular intake of glucose in muscle and adipose tissue. Increased amino acid uptake forces cells to absorb circulating amino acids.
Increase of DNA replication and protein synthesis

Decreased gluconeogenesis decreases production of glucose from non-sugar substrates, primarily in the liver (vast majority of endogenous insulin arriving at the liver never leaves the liver)
lack of insulin causes glucose production from assorted substrates in the liver and elsewhere.

Increased glycogen synthesis insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen
lowered levels of insulin cause liver cells to

convert glycogen to glucose and excrete it into the blood. This is the clinical action of insulin, which is directly useful in reducing high blood glucose levels as in diabetes.

Decreased proteolysis decreasing the breakdown of protein. Increased lipid synthesis insulin forces fat cells to take in blood lipids, which are converted to triglycerides. Increased esterification of fatty acids forces adipose tissue to make fats (i.e., triglycerides) from fatty acid esters. Decreased lipolysis forces reduction in conversion of fat cell lipid stores into blood fatty acids

Increased potassium uptake

forces cells to absorb serum potassium. Insulin's increase in cellular potassium uptake

lowers potassium levels in blood.

Occurs via insulin-induced translocation of the Na+/K+ATPase to the surface of skeletal muscle cells.

Lack of insulin inhibits absorption. Arterial muscle tone forces arterial wall muscle to relax, increasing blood flow, especially in micro arteries; This lack of insulin reduces flow by allowing these muscles to contract.

Increase in the secretion of hydrochloric acid by parietal cells in the stomach

Decreased renal sodium excretion.

Decrease Blood Glucose Concentration Promote Glycogen Formation Inhibits Glycogenolysis Inhibits Gluconeogenesis

Liver

Adipose Tissue

Muscle

Glycogen

Glucose

Glucose-6Phosphate

Glucose

Pyruvate

Increase Anabolic Protein Synthesis Inhibits Protein Degradation

Muscle

Liver

Amino Acid

Decrease Blood Fatty Acid and Ketoacid Concentration Inhibits Lypolysis

Liver

Adipose Tissue

Fatty Acid Ketoaci d

Insulin Deficiency (and glucagon excess)

Increase lipolysis

Decrease Glucose uptake

Increase Glucose Production

Increase plasma FFA,,ketogenesis, ketonuria ketonemia

Hyperglycemia, , Glycosuria,, Osmotic diuresiss, Electrolyteb depletion

Dehydration, acidosis

Coma, Death

Polyuria up to 6-8 L day; nocturia dehydration,hypotension Polydipsia- enormous taste but intake less than output Polyphagia- excessive food intake but with weight loss, weakness irritability

Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. Several distinct types of DM are caused by a complex interaction of genetics and environmental factors.

Type 1 DM is the result of complete or neartotal insulin deficiency Aka juvenile diabetes Is also termed insulin dependent diabetes mellitus most commonly in childhood or adolescence

Type 2 DM is a heterogeneous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion, and increased glucose production. preceded by a period of abnormal glucose homeostasis classified as impaired fasting glucose (IFG) or impaired glucose tolerance (IGT).

Insulin resistance and abnormal insulin secretion are central to the development of type 2 DM. Sometimes called age-onset or adult-onset diabetes Type II is considered a milder form of diabetes because of its slow onset

Normal value: 70 100 mg/dl

With meal: 135 140 mg/dl

Normal blood values for a 75-gram oral glucose tolerance test used to check for type 2 diabetes in those who are not pregnant:

Fasting: 60 -100 mg/dL 1 hour: less than 200 mg/dL 2 hours: less than 140 mg/dL
Note: mg/dL = milligrams per deciliter

 Diabetic:

Fasting > 120 2 hours after glucose > 180

An HbA1c of 5.6% or less is normal. The following are the results when the HbA1c is being used to diagnose diabetes:
Normal: Less than 5.7% Pre-diabetes: 5.7% to 6.4%

Diabetes: 6.5% or higher