Exam 4: Diabetes Flashcards
Binding of insulin to receptor causes:
Phosphorylation of receptor and IRS-1 (insulin receptor substrate)
GLUT4 is:
Glucose transporter on somatic cells activated by insulin
Non-glucose substances brought into the cell by insulin’s action:
Amino acids
K+
PO4-
Mg++
Insulin’s effects on the nucleus:
Synthesis of various enzymes suppressed/induced
Cell growth regulated by IREs (insulin responsive elements); mostly signals ATP/glycogen
Insulin is a strong growth factor!!
Effects of insulin:
↓ appetite, glucagon
↑ glucose uptake, glycolysis, glycogen synthesis, TG synthesis, amino acid uptake, protein synthesis
Effects of lacking insulin:
↑ appetite, glucagon, blood glucose, gluconeogenesis, lipolysis, protein breakdown, glycogenolysis, ketone body production
↓ glucose uptake, protein synthesis
Effect of insulin on fat:
Fat takes up glucose, converts it to more fat for later us
Effect of insulin on muscle:
Muscle takes up glucose, stores it mostly as glycogen and triglycerides
Also makes ATP/protein synthesis
Effect of insulin on liver:
Liver takes up glucose, makes glycogen, and stores it
Also makes proteins
Effect of low glucose on the pancreas:
Pancreas releases glucagon
Effect of glucagon on the liver:
Signals liver to break down glycogen, release glucose, and make new glucose (gluconeogenesis)
Effect of glucagon on muscle:
Minimal effect, though will tell muscle to break down protein and release amino acids
Effect of glucagon on fat:
Fat breakdown, free fatty acids and glycerol into blood
Distribution of exocrine/endocrine functions in the pancreas:
Exocrine more in the head (digestive functions)
Endocrine functions more in the tail
In diabetes, when glucose is high, insulin and glucagon are:
Both are low
Role of β cells:
Insulin production, stimulated by glucose
Role of α cells:
Produce glucagon
Effect of insulin secretion on α cells:
Inhibits glucagon secretion
Effect of glucose on α cells:
None
Role of δ cells:
Produce somatostatin
GLUT2 is:
Glucose transporter on β cells
Mechanism by which glucose triggers β cell insulin release:
- Glucose entry via GLUT2 leads to ATP production
- ATP-gated K+ channel prohibits K+ outflow and depolarizes cell
- Voltage-gated Ca++ channel allows Ca++ influx
- Ca++ triggers insulin release from storage vesicles
Blood glucose range where insulin balances glucagon:
80-100
Describe MODY:
Maturity-Onset Diabetes of Youth; genetic defect in insulin production/release
Tx for MODY:
Oral drug for DMII to promote insulin release
Effect of Cushing’s on blood sugar:
↑ blood sugar from ↑ cortisol
Effect of acromegaly on blood sugar:
Growth hormone ↑ blood sugar
Effect of pheochromocytoma on blood sugar:
Epi/NE ↑ blood sugar
Diabetes is usually triggered during a time of:
Hormone flux
Mechanism by which insulin secretion ↓ in DM II:
Persistent leftover glucose in blood causes toxicity of β cells, which ↓ insulin production and ↑ resting blood sugar
Mechanism by which insulin secretion ↓ in DM II:
Persistent leftover glucose in blood causes toxicity of β cells, which ↓ insulin production and ↑ resting blood sugar
Clinically typical DM I patient:
Young, normal/skinny, with ↓ blood insulin, anti-islet cell antibodies, and ketoacidosis
Clinically typical DM II patient:
Older, obese, ↑ blood insulin, no anti-islet cell antibodies, and not in ketoacidosis
Clinical diagnosis of DM:
Fasting BG > 126 or
plasma glucose > 200 after 2 hrs during OGTT
Glucose levels in pregnancy are:
Normally lower
Clinical diagnosis of gestational diabetes:
FBG > 95
OGTT 1-hr > 180
OGTT 2-hr > 155
OGTT 3-hr > 140
Gestational diabetes typically develops:
24-28 weeks gestation
Complications seen in babies of mothers with gestational diabetes:
Hyperglycemia
HTN
Cardiovascular complications
Alternate terms for pre-diabetes:
Impaired fasting glucose
Impaired glucose tolerance
Clinical diagnosis of IFG:
FBG 100-125
Clinical diagnosis of IGT:
BG 140-199 after 2-hr OGTT
Prevention of DM II from pre-diabetes:
Walking! Activity, diet
Acute complications of diabetes:
Hypoglycemia (DM I)
DKA (DM I)
HHNKS (DM II)
Describe HHNKS:
BG is so high it acts as an osmotic agent and draws water out of cells - coma/death from neuron shrinkage
Describe AGEs:
Advanced Glycosylation End-Products; glucose sticks to proteins and doesn’t let them work properly
Examples of microvascular disease:
Diabetic retinopathy
Diabetic nephropathy
Diabetic cardiomyopathy
Examples of macrovascular disease:
Coronary artery disease
Stroke
PAD
Examples of increased activity of polyol/sorbitol pathway:
Diabetic neuropathy - Schwann cells become swollen and damage axons
Cataracts
Examples of increased activity of polyol/sorbitol pathway:
Diabetic neuropathy - Schwann cells become swollen and damage axons
Cataracts
S/s of mild hypoglycemia:
Hunger Shakiness Paleness Blurry vision Sweating Anxiety
S/s of severe hypoglycemia:
Extreme fatigue Confusion Dazed appearance Seizures Unconsciousness Coma Death
Pathogenesis of DKA:
↓↓ glucose = ↑↑ glucagon
Uncontrolled fat metabolism → ketone production
Life-threatening hyperglycemia
S/s of DKA:
Fruity acetone breath Kussmaul breathing Dehydration N/V, abdominal pain ∆LOC, weakness, parasthesia
Lab changes in DKA:
↑↑ BG
Electrolyte imbalances
Metabolic acidosis
+ ketones in urine
Filtered load =
Plasma concentration * GFR
Normal GFR:
125 ml/min
Renal threshold for glucose:
300 mg/min
1 mM glucose = _____ mg/dL
18
1 mM glucose = _____ mg/dL
18
Why is acetyl-CoA converted to ketone bodies?
During periods of gluconeogenesis, oxaloacetate is used up and Kreb’s cycle cannot run; acetyl-CoA builds up and is converted into ketone bodies that the brain can use
Three example ketone bodies:
Acetoacetate
Acetone
β-hydroxybutyrate
Organs able to use ketone bodies for energy:
Brain
Heart
Kidney
Liver
Why is acetyl-CoA converted to ketone bodies in DKA?
During periods of gluconeogenesis (since glucose cannot get into the cells), oxaloacetate is used up and Kreb’s cycle cannot run; acetyl-CoA builds up and is converted into ketone bodies that the brain can use
Organs able to use ketone bodies for energy:
Brain
Heart
Kidney
Liver
Only true ketoacid of the ketone bodies:
Acetoacetate
pH in DKA vs. HHNKS:
Lower/worse acidosis in DKA
Ketone bodies in DKA vs. HHNKS:
Much more ketone bodies in DKA
C-peptide in DKA vs. HHNKS:
Much higher in HHNKS; indicative of how much insulin is being made
Anion gap in DKA vs. HHNKS:
Much higher in DKA due to ketoacids
Effects (3) of AGEs on proteins:
Cross-link polypeptides of the same protein; makes collagen brittle
Traps non-glycosylated proteins
Confers resistance to proteolytic digestion
Non-protein effects of AGEs:
Induce lipid oxygenation
Inactivate NO
Bind nucleic acids
Gestational diabetes is probably caused by:
Chorionic somatomammotropin
Products of glucose on the way to becoming AGEs:
Schiff bases
Amadori products
Effects of AGEs binding to RAGEs:
Monocyte emigration Cytokine/growth factor secretion Vascular permeability Procoagulant activity Cellular proliferation ECM production
Basically… inflammation
HbA1c is:
Glycosylated hemoglobin; also an Amadori product; hemoglobin with AGEs stuck to it
Pathogenesis of diabetic retinopathy:
Arterioles in eye leak fluid into retina and cause degradation
Prevalence of diabetic retinopathy:
40% in type I
20% in type II
Early stage of diabetic retinopathy:
Background diabetic retinopathy; small, dot hemorrhages
Late stage diabetic retinopathy:
Proliferative diabetic retinopathy; ischemic areas in retina, neovascularization, hemorrage of delicate new vessels
Effects of diabetic nephropathy on the kidney:
Glomerular leakiness → proteinuria
Glomerulosclerosis
Tubulointerstitial fibrosis
Arteriolar sclerosis
Changes seen in diabetic nephropathy in the glomerulus:
Increased mesangial matrix (2/2 growth factor from macrophages)
Nodular lesions
Microaneurysms → fibrin clots/caps
Fastest progression of diabetic nephropathy seen in:
Pts with poorly controlled HTN
Tx of diabetic nephropathy:
ACEIs/ARBs to keep HTN under control; dialysis when needed
Negative sequelae of diabetic neuropathy:
Unawareness of wounds/infection leading to uncontrolled infection
