Glucose Homeostasis, Diabetes Mellitus Flashcards
Pancreas
- Elongated organ posterior to stomach
- Performs both exocrine and endocrine activities
- 99% of cells are clustered acinar cells (exocrine)
– Synthesizes digestive enzymes
– Secreted through pancreatic ducts into small intestine - 1-2 million tiny clusters of cells form pancreatic islets (endocrine)
– aka Islets of Langerhans
Pancreatic Islets
- Alpha cells (17%) secrete glucagon
- Beta cells (70%) secrete insulin
- Delta cells (7%) secrete somatostatin
- Pancreatic polypeptide (6%) cells secrete pancreatic polypeptide
GLUT-2
– Independent of insulin
– Pancreas
– Liver
GLUT-4
– Dependent on insulin
– Skeletal muscle
– Adipose tissue
Insulin
- Secreted by beta cells
- Stimulus: Increased blood levels of glucose
– Humoral - Targets have a tyrosine kinase receptor (RTK)
– Non-G-protein transmembrane receptor - Target: Liver
– Action: Stimulates glycogenesis - Target: Skeletal muscle
– Action: Glucose uptake
– Action: Amino acid uptake
– Action: Stimulates glycolysis
– Action: Stimulates glycogenesis
– Action: Stimulates protein synthesis - Target: Adipose tissue
– Action: Glucose uptake
– Action: Stimulates lipogenesis - Net effect: Decreased blood glucose levels
Absorptive (Fed) State
- First four hours after a meal
- Insulin stimulates enzymes needed for anabolism
– Carbohydrates
▪ Glycogenesis: glucose is converted into glycogen
– Lipids
▪ Lipogenesis: fatty acids are converted into triglycerides
– Proteins
▪ Protein synthesis: amino acids are converted into proteins - Insulin inhibits enzymes needed for catabolism
– Decreases glycogenolysis, lipolysis, proteolysis - Insulin inhibits gluconeogenesis
Growth Hormone
– Target: Skeletal muscle
▪ Decrease glucose uptake
– Target: Adipose tissue
▪ Stimulates lipolysis
– Target: Liver
▪ Stimulates gluconeogenesis
Excess GH causes hyperglycemia
– Results in increased insulin secretion
– May cause “beta-cell burnout”
– Called a diabetogenic effect
IGF
– Target: Skeletal muscle
▪ Increased glucose uptake
▪ Increase amino acid uptake
▪ Increased protein synthesis
– Target: Adipose tissue
▪ Increased glucose uptake
GH’s synergistic effects
– Works indirectly via IGF
▪ IGF has similar structure to insulin
▪ IFG receptor similar to insulin
receptor
– IGF increases glucose uptake
▪ Skeletal muscles and adipose tissue
– IGF increases amino acid uptake
▪ Skeletal muscles
– Protein Anabolism
▪ IGF stimulates protein synthesis
GH’s antagonistic effects
– Works directly on target cells
– Carbohydrate catabolism
▪ GH stimulates glycogenolysis
– GH decreases glucose uptake
▪ Skeletal muscle and adipose tissue
– GH stimulates gluconeogenesis
– Lipid catabolism
▪ GH stimulates lipolysis
Glucagon
- Secreted by alpha cells
- Stimulus: Decreased blood levels of glucose
– Humoral - Targets have a Gs protein coupled receptor
- Target: Liver
– Stimulates glycogenolysis
– Stimulates gluconeogenesis - Target: Adipose tissue
– Stimulates lipolysis - Note: Glucagon does not have receptors on
skeletal muscle
– Skeletal muscle is NOT a target - Net effect: Increased blood glucose levels
Glucagon Hormonal Interactions
- During nonemergent situations:
– Glucagon & Insulin = Antagonistic - In response to physiological stresses:
– Glucagon & Epinephrine = Synergistic
▪ Both glucagon and epinephrine stimulate adenylate cyclase pathway
– Glucagon & Cortisol = Permissive
▪ Thyroxine increases number and sensitivity of glucagon receptors
– Glucagon & Thyroxine = Permissive
▪ Thyroxine increases number and sensitivity of glucagon receptors
Postabsorptive (Fasting) State
- More than 4 hours after a meal
– Blood glucose levels fall as glucose leaves bloodstream to enter body cells while
none is being absorbed from digestive tract - Glucagon stimulates enzymes needed for catabolism
– Carbohydrates
▪ Glycogenolysis: glycogen is broken down into glucose
– Lipids
▪ Lipolysis: triglycerides are broken down into fatty acids - Glucagon inhibits enzymes needed for anabolism
– Decreases glycogenesis and lipolysis - Glucagon stimulates gluconeogenesis
– New glucose molecules are formed from non-carbohydrate sources
▪ Amino acids and lipids
Diabetes Mellitus
- Chronic condition in which pancreas does not produce sufficient
insulin or body cells do not use insulin properly - Affects over 30 million people in the US
- 4th leading cause of death, mainly due to damage to blood vessels
- Leading cause of retinal blindness, kidney failure, and
nontraumatic amputations in the United States - Associated with increased heart disease and stroke
Diagnosing Diabetes Mellitus
- Expected values for normal fasting blood glucose concentrations is
70 – 100 mg/dL
– Fasting = no eating for at least 8 hours - Major hallmark of diabetes mellitus is hyperglycemia
– High blood glucose levels - Prediabetes = blood glucose levels between 100 to 125 mg/dL
– HbA1C between 5.7 – 6.4 % - Diabetes is diagnosed of patient has one of the following:
– Fasting glucose ≥ 126 mg/dL on two separate occasions
– Random plasma glucose > 200 mg/dL on two separate occasions
– Symptoms of diabetes (e.g., polyuria, polydipsia, ketoacidosis) + random
plasma glucose > 200
– HbA1C > 6.5%
Blood glucose meters (finger prick)
– Provide an instant, single time point of blood glucose level
– Using a lancet, a drop of blood is placed on a strip attached to a glucometer
– Fasting blood glucose test
▪ Measures blood glucose after an overnight fast
▪ Normal is 70-100 mg/dL
– Random blood sugar test
▪ Measures blood glucose at any time, with or without fasting
▪ Normal is about 70-180 mg/dL
Glycosylated hemoglobin A1C (HbA1C) test
– Provides a measure of glucose control over a 2-3 month period
– Blood is drawn at a clinic/hospital and sent to a lab for testing
– Normal is less than 5.7%
Continuous glucose monitoring (CGM)
– Provide a delayed, but continuous glucose levels
– Measures glucose in interstitial fluid (not blood)
– Sensor is placed on body and continuously detects glucose levels
– Sensor is connected to a device (usually wireless) that records readings
Other symptoms
– Fatigue
▪ Cells are unable to make ATP without glucose
– Unexplained weight loss
▪ In the absence of glucose, body cells will metabolize fat and muscle for energy
– Glaucoma
▪ Hyperglycemia in eye prevents proper fluid drainage and leads to increased pressure on retina
– Cataracts
▪ Increased sugar in blood may create a cloudy buildup in the eye’s lens
– Irritability, trouble thinking clearly, anxiety
▪ Brain is most-energy demanding organ; without glucose
– Frequent infections and slow-healing cuts and sores
▪ Reduced white blood cell response and increased immune disfunction
– Ketone bodies in urine and ketoacidosis
▪ Ketones are a byproduct of fatty acid metabolism, which increases with diabetes
Symptoms of Diabetes Mellitus
- Polyuria (frequent urination)
– Excess glucose lost in urine acts to pull fluid into urine by osmosis
– Abnormal loss of fluid in urine; body is dehydrated - Polydipsia (increased thirst)
– Hyperglycemia leads to hyperosmolarity (blood is hypertonic) - Polyphagia (increased hunger)
– Cells are unable to normally absorb glucose into their cells
– Increased proteolysis and lipolysis
Acute Complications of DM (Hyperglycemic Crises)
- Metabolic emergencies that may result in hospitalization and/or death
- Increased gluconeogenesis results in hyperglycemia and hyperosmolarity of ECF
- Both conditions show symptoms related to hyperglycemia
– Polydipsia, Polyuria, Polyphagia
Diabetic Ketoacidosis (DKA)
– Usually seen in DM type I
– Symptoms usually present within a few hours
– Without glucose, cells break down fatty acids for energy
▪ Ketones are produced as byproducts of fatty acid breakdown
▪ Ketones are acidotic and rapidly decrease blood pH (potentially fatal)
▪ Patients compensate low pH with deep fast breathing (Kussmaul breathing)
Hypoglycemia
– Glucose levels below 60 mg/DL
– Numerous causes
▪ Insulin overdose, prolonged exercise, alcohol use, liver or kidney dysfunction
▪ Deficiency of glucocorticoids or growth hormone, genetics
– Brain cells are deprived of glucose needed to function effectively
– Symptoms include mental disorientation, convulsions, unconsciousness,
insulin shock, or death
– Glucagon given if individual unconscious and unable to eat
* Symptoms of hypoglycemia are similar to hyperglycemia
– Important to correctly identify cause of symptoms and treat appropriately
* Hyperinsulinism – most often occurs when diabetic injects too much insulin
– Stimulates secretion of epinephrine, glucagon, and growth hormone
– Main symptom is hypoglycemia (decreased blood glucose levels)
