Effects of insulin Flashcards
Effects of insulin within cell
3 effects of insulin on the liver
- Increased glycogen synthesis 2. Increased glycolysis 3. Decreased gluconeogenesis
3 effects of insulin on fat
- Increased glucose transport 2. Increased lipogenesis 3. Decreased lipolysis
3 effects of insulin on skeletal muscle
- Increased glucose transport (= fat) 2. Increased glycogen synthesis (= liver) 3. Decreased gluconeogenesis
What receptors does the heart have
GLUT 1 & some GLUT 2
=> heart gets a low level of glucose all of time even in the absence of insulin
Effect of insulin on glycogen metabolism (in hepatocytes)
see folder
Insulin regulated metabolism in an adipocyte
see folder
Relationship between EC & IC glucose and insulin
Linear relationship (graph)
- What does insulin stimulate (5) 2. What does insulin inhibit (5)
Image
What is the structure of glucagon
Peptide hormone 29 AAs
What is glucagon produced by
Alpha cells -20%
What is the half life of glucagon
5-10 mins degraded by liver tissue
3 factors that increase glucagon secretion
- Blood glucose < 70 mg/dL 2. AAs (high protein, low CHO meal) 3. Stress - adrenaline via beta-adrenergic receptors on alpha cells
2 factors that decrease glucagon secretion
- Increase blood glucose 2. Insulin (feed-forward mechanism)
Target tissues of glucagon
Liver muscle adipose tissue
What is the mechanism of action of glucagon
Binds to Gs-coupled receptor, resulting in increased cAMP and increased PKA activity - also activated IP3 pathway => increase in Ca2+
Action of glucagon on the liver (3)
PRIMARY TARGET - increase blood glucose
- Increased glycolysis - Activates a phosphorylase - cleaves a 1-P off glycogen
- Inhibits glycogenesis - Inactivates glycogen synthase by phosphorylation
- Increased gluconeogenesis - Increases phosphoenolpyruvate carboxykinase
Action of glucagon on lipids
Increases lipolysis - activates lipases - breaking down of triglycerides
- inhibits acetyl CoA carboxylase - stops FFA from becoming acetyl CoA
Glucagon action on cells
see folder
Response to decreasing glucose levels
photo
Where was somatostatin first discovered and where is it found now
Hpothalamus - GHIH
Pancreas, intestinal tract, CNS
What does somatostatin do
Inhibits secretion of many other hormones: 1. GH 2. Insulin 3. Glucagon 4. Exocrine pancreatic secretions
What are the 2 forms of somatostatin
SS-14 & SS-28
Tissue-specific isoform of SS-14
Sole isoform from pancreas Major isoform in CNS
Tissue-specific isoform of SS-28
Major isoform in intestine
Which SS isoform is more potent in inhibition of GH secretion
SS-28
Which SS isoform is more potent in inhibition of glucagon release
SS-14
What are the microvascular complications of diabetes (4)
- Diabetes eye disease (retinopathy & cataracts) 2. Renal disease 3. Erectile dysfunction 4. Peripheral neuropathy
What are the macrovascular complications of diabetes (4)
- Stroke
- Heart disease & hypertension - 2-4x increased risk
- Peripheral vascular disease
- Foot problems
Type I diabetes mellitus/Insulin dependent/Juvenile onset
5-10% of all DM Absolute insulin deficiency Pancreatic cell destruction photo
Type II diabetes mellitus/non-insulin dependent/Adult onset
Insulin resistance Can lead to beta cell exhaustion resistance to insulin begins 10 yrs before diagnosis most common in those > 40 (children being diagnosed more regularly) photo
Where are Glucagon-Like Peptide 1 receptors located
L-cells located primarily in distal ileum & colon but also jejunum & duodenum
What accounts for 90% of the incretin effect
Glucose Dependent Insulinotrophic polypeptide (K cells intestinal epithelia - mainly duodenum epithelia)
Glucose stimulated secretion of insulin
photo
Pathophysiology of type 2 diabetes
- Insulin resistance 2. Incretin effect 3. Relative insulin deficiency
Contents of posionous venom of gila monster
- serotonin - hyaluronidase - phospholipases/diesterases - proteases
What is the biologically active peptide associated with gila monster
Exendin-4
What does exendin-4 do
Interacts with the GLP-1 receptor stimulates insulin release - over stimulation of pancreas in vivo - Development of synthetic exendin-4 BYETTA as a treatment of diabetes
Pre-receptor resistance
ANTIBODIES TO INSULIN
No insulin receptor binding
MUTANT INSULIN STRUCTURE
Beta chain mutations - inactive
FAMILIAL HYPERPROINSULINEMIA
Increase in proinsulin - inactive
Receptor resistance
- Decrease in insulin receptor number/receptor affinity for insulin
- Mutation or auto-antibody to insulin receptor
Post receptor resistance
Down regulation of beta-cell glucose transporters
MODY - Mature Onset Diabetes of the Young
Group of monogenic disorders characterised by autosomal dominantly inherited non-insulin dependent form of diabetes classically presenting in young adults before the age of 25 years - 2-5% of diabetics
MODY 1
HNF4A
Transcription factor; decreased insulin secretion
MODY 2
GCK
Decreased glucose sensitivity due to phosphorylation defect; decreased glycogen storage
MODY 3
HNF1A
Transcription factor; decreased insulin secretion, progressive beta cell damage
MODY 4 (not as common)
PDX1/IPF1
Impaired pancreas development; homozygotes experience pancreas agenesis
MODY 5
HNF1B
Transcription factor; decreased insulin secretion
DIABETES - disease of the 3 Polys
POLYPHAGIA
No glucose entering cells => hunger
Hyperglycemia - increased blood glucose
Glucosuria - Glucose Tmax exceeded in kidney => glucose lost in urine
POLYURIA
Glucose drags water into urine
POLYDIPSIA
Increased thirst to replace water loss
