Pancreas, Insulin, Glucagon

Question 1

importance of blood sugar

Answer 1

• essential for brain function in vertebrates

- stability of blood sugar through range of activities and demands is insulin’s responsiblity

Question 2

Banting and Best

Answer 2

• created diabetes in dogs by disabling pancreas
• reversed diabetes in dogs by providing extracts of pancreatic products
• discovered heparin

Question 3

pancreas physiological anatomy

Answer 3

• composed of acini (secrete digestive juices) and islets of langerhans (secrete insulin and glucagon directly into blood)
• islets have alpha, beta and delta cells
• beta cells secrete insulin and amylin
• alpha cells secrete glucagon
• delta cells secrete somatostatin

Question 4

insulin receptor

Answer 4

• transmembrane receptor: 2 a, 2 b subunits
• b subunits autophosphorylate intracellularly
• tyrosine kinase activity
• when insulin is increased, blood sugar decreases

Question 5

metabolic effects of insulin: carbs

Answer 5

• when you eat high carb meal, insulin causes muscle, adipose and others to take up glucose
• uptake of glucose by facilitated diffusion (hexose transporters)
• transporters (GLUT4) incorporated in vesicles when insulin is low
• brain and liver use non-insulin dependent transporter
• insulin promotes glycogen storage by activating hexokinase but inhibiting glucose 6-phosphate
• sweets = bread, rice, pasta, potatoes

Question 6

metabolic effects of insulin: fats

Answer 6

• when liver is saturated with glycogen, hepatocytes shunt glucose to fatty acid synthesis, exported as lipoproteins
• adipocytes use FA to synthesize triglycerides, insulin inhibits enzymes that break down tryglycerides

Question 7

metabolic effects of insulin: proteins

Answer 7

• promotes incorporation of amino acids into cells

- protein degradation when insulin levels are low

Question 8

metabolic effects of insulin: Na/K pumps

Answer 8

• activated by insulin - increases potassium within cells
• in DKA patient insulin administration can dramatically lower blood K levels causing death –> give insulin SLOW - too much will tank potassium and cause cardiac arrhythmias

Question 9

6th leading cause of death by disease

Answer 9

• diabetes
• 18M+ Americans have it
• 200,000 annual deaths

Question 10

MCC blindness in adults

Answer 10

-diabetes

Question 11

insulin

Answer 11

lowers BG by increasing transport to muscle, liver, adipose

Question 12

glucagon

Answer 12

increases BG by stimulating gluconeogenesis, glycogenolysis

Question 13

somatostatin

Answer 13

• inhibits GH, TSH

- delays intestinal absorption of Glucose

Question 14

Classification of diabetes

Answer 14

• Type 1 (IDDM)– b cell destruction by autoimmunity or idiopathic cause
• Type 2 (NIDDM)– disorder of insulin resistance, secretory disorder possible (90-95%) –> You make insulin but your body doesn’t respond to it
• Other forms include genetic defects in beta function, insulin action, CF, Cushing, drug effects, infections
• GDM –> Gestational DM
• Its normal to see blood sugars climb as people age
• Juvenile diabetes no longer a thing

Question 15

T1DM 1A vs 1B

Answer 15

• 1A = immune mediated –> autoimmune destruction
• 1B = idiopathic –> cant identify why it happens
• 95% have 1A

Question 16

Pathophys of T1DM

Answer 16

• glucose accumulates in the blood because you don’t have insulin
• ketoacidosis common
• insulin inhibits lipolysis and fatty acid metabolism, therefore pts typically thin bc these pts dont have insulin
• test by detection of autoantibodies to insulin (IAA), glutamic acid decarboxylase (GAD), tyrosine phosphatase (IA-2)

Question 17

T2DM

Answer 17

• hyperglycemia and relative insulin deficiency (high, normal, or low)
• not associated with autoimmunity –> not a production problem, a response problem
• most pts obese –> insulin inhibits fatty acid metabolism, also NO KETOACIDOSIS!!!
• insulin is usually high at diagnosis! –> insulin inhibits lipolysis so they typically present as obese - obesity is probably a contributing factor to and product of type 2

Question 18

pathophys of T2DM

Answer 18

• impaired beta fn
• impaired insulin secretion
• peripheral insulin resistance
• increased glucose production (hepatic)
• initial hyperinsulinemia in response to insensitivity, eventual fatigue of beta cells (their insulin levels may be low and their glucose high which may make them look like T1DM)

Question 19

relationship of DM to metabolic syndrome

Answer 19

• high triglycerides
• low HDL
• HTN
• inflammation
• fibrinolysis
• Abn vascular endothelium
• macrovascular dz
• central obesity

Question 20

free fatty acid theory

Answer 20

-central obesity causes increased FFA, fasting and postprandial
-stimulate beta cell production, leads to lipotoxicity
cause insulin resistance and glucose underutilization at periphery
-FFA and TG reduce hepatic insulin sensitivity, leading to gluconeogenesis (if liver cant incorporate sugar, it makes sugar)
-diversion of FFA to non-adipose sites

Question 21

GDM

Answer 21

• glucose intolerance to various degrees in 1-14% of pregnancies
• hx of DM, glycosuria, stillbirth, obesity, AMA, G5+
• fetal risks: macrosomia, shoulder dystocia, hypoglycemia, hypocalcemia, polycythemia, hyperbilirubinemia
• tx with insulin - not PO meds

Question 22

s/sx GDM

Answer 22

• 3 Ps - polyuria, polydipsia, polyphagia
• wt loss with T1DM
• blurred vision
• fatigue
• paresthesias –> not a presenting sx of diabetes
• skin infections
• lipemia

Question 23

3 issues that cause the 4 leading causes of death

Answer 23

-smoking, sedentary lifestyle, poor nutrition

Question 24

testing for DM

Answer 24

• blood sugar (FBS, RBS)
• GTT
• Glycated Hemoglobin (Hgb, A1c)
• UA
• glucose needs to be 150-180 in order to show up on dip

Question 25

management of DM

Answer 25

- diet and exercise --> when you use muscles, they draw more sugar - routine blood testing - insulin --> the most important drug you need to give - oral medications for type 2 (sulfonylureas = insulin secretagogues, repaglinide/nateglinide, biguanides = metformin = DOC FOR T2DM!, alpha glucosidase inhibis, thiazolidinedione

Question 26

Acute complications of DM

Answer 26

- DKA (beta hydroxybutyrate, acetoacetate, acetone0 - hyperosmolar hyperglycemia - hypoglycemia

Question 27

chonic complications of DM

Answer 27

- neuropathy --> feet get hit first because neurons that take info from toes and feet are really long and big so they get affected first because there is more real estate to hit - GI motility - nephropathy - retinopathy - macrovascular changes - foot ulcers --> all diabetics need feet checked - infection

Question 28

hyperglycemia hyperosmolar non-ketotic syndrome

Answer 28

- BG usually >600 - hyperosmolarity, dehydration, depressed sensorium, acute pancreatitis, severe infection, MI - NO KETOACIDOSIS - prognosis worse than DKA

Question 29

ketoacidosis

Answer 29

- fatty acid metabolism produces ketones - used by brain and muscle - usually type 1, can occur late in 2 - with acidosis, Na dumped, K retained - Presents with dehydration, n/v, fruity odor, Kussmaul breathing, abdominal pain, mentation changes, hyperglycemia, hyperkalemia - underlying illness common

Question 30

diabetic coma

Answer 30

- result of prolonged blood sugar extreme | - caused by DKA (type I), HHS (sugar in urine draws water from body, BS>600), hypoglycemia