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What percent of the pancreas is endocrine compared to exocrine
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Hypoglycemia for an extended period of time can have what effects
- Neurological problems
- Coma
- Quick Death
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What is considered hyperglycemic and hypoglycemic
- Hyper - Glucose above 110mg/100mL
- Hypo - Glucose below 60mg/100mL
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What are the major types of nutrient substances
- Carbohydrates
- Fats
- Proteins
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Where are most of the carbohydrates and fats eventually excreted
Lungs
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What substrates are metabolized directly for energy
Carbohydrates and fats
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What tissues are involved in substrate interconversions
- Adipose tissue
- Liver
- Muscle
- Kidney
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What systems are the interconversion of substrates regulated by
- Endocrine system
- Sympathetic Nervous system
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How long do the absorptive and Post absorptive states last, and what are their main sources of energy
- Absorptive - 60min (Glucose is main energy source)
- Post Absorptive - 2+ hours (Fat is the main source)
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What factors regulate insulin release from pancreatic beta cells
- GI hormones (+)
- Increase in amino acids (+)
- Increase in Glucose (+)
- Parasympathetic nervous system (+)
- Sympathetic nervous system (-)
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What cells secrete insulin
Beta cells in the pancreas
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How does an insulin secretion curve present over sixty minute period following a meal
There is an initial spike of insulin in the blood as a result of the stored insulin released, then a significant dip followed by a gradual increase as a result of synthesis of new insulin
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What is the sequence that leads to insulin release following glucose uptake
- GLUT2 glucose transporter shunts glucose into the B cell
- Glucokinase phosphorylates the glucose to Glucose 6-P
- Glycolysis converts the Glucose 6-P into ATP
- ATP stops the K+ channel causing depolarization of the cell
- Calcium channels open filling the cell with Ca+
- Calcium channels cause the bursting of the insulin storage granules releasing insulin into the blood
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How do GLUT1, 2, and 4 differ
- GLUT1 - Found in the brain (insulin sensitive)
- GLUT2 - Found in liver beta cells (not sensitive to insulin)
- GLUT4 - Found in adipose tissue, and muscle (insulin sensitive)
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What is unique about insulin transport in the blood
It is a water soluble peptide and therefore doesn't require transporters to carry it
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What receptor mechanism does insulin activate once it binds
Tyrosine kinase to initiate cellular responses
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Insulin has what effect on GLUT4
When insulin receptors are activated, they recruit GLUT4 transporters from vescicles in muscle and adipose tissue
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Lipoprotein Lipase (LPL) synthesis, activity, and movement to the surface of endothelial cells is activated by
Insulin stimulation on the Adipose cells GLUT4 receptor
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What actions does insulin have on muscle cells
- It recruits GLUT4 receptors from vesicles and increases;
- Protein synthesis /Decrease degradation
- Amino acid uptake
- Glycogen synthesis
- Glucose transport
- Decrease in Glycogenolysis
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What kind of glucose receptors are on hepatocytes
GLUT2 (not insulin sensitive)
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What is the action of insulin on the hepatocytes
- Shuts off Gluconeogenesis, Glycogenolysis, and lipolysis
- Increases Lipogenesis, and glycogen synthesis
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What is the effect of insulin on adipose tissue
- A decrease in Glycogenolysis, and Lipolysis
- Increase in Glucose transport, Glycogen synthesis, Lipogenesis
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Glycogenolysis
Coversion of glucogen to glucose stimulated by Glucagon or Epinephrine
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Ketogenesis
Process of making ketone bodies from the breakdown of fatty acids
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What is the net result of insulin on Lipid metabolism in the blood
A decrease in both plasma free fatty acids and ketogenesis (ketones in the blood)
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What is the net result of insulin on Protein metabolism in the blood
Decrease in plasma amino acids and urinary nitrogen creating a positive nitrogen balance
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Alpha cells in the pancreas secrete
Glucagon
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What causes the release of glucagon
- A decrease the plasma glucose
- An increase of amino acids in plasma
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What is the general action of Glucagon on adipose tissue
Increase in lipolysis
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What is the effect of Glucagon on the liver
Increase in; Lipolysis, Gluconeogenesis, Glycogenolysis
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What is the effect of Glucagon on pancreatic Beta cells
Increase in the release on insulin (indirectly)
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What is the cellular response in the liver to Glucagon
- G cell receptor is activated
- Adenylyl cyclase is stimulated
- cAMP is formed
- Phosphorylase b is converted to its active form "a"
- Glycogenolysis and Gluconeogenesis take place
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What is the cellular response of adipose tissue to Glucagon
- G cell receptor activated
- Adenylyl cyclase stimulated
- cAMP formed
- PKA activates lipase
- Lipolysis begins
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What happens to the levels of Glucagon and insulin after a meal
Glucagon lowers and Insulin elevates
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Epinephrine release in regard to energy metabolism is stimulated when
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What is the effect of stress and hypoglycemia on energy metabolism
It increases the amount of epinephrine which stimulates Glucagon release, Gluconeogenesis, Glycogenolysis, Lipolysis, and has an indirect inhibition on insulin secretion
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Cortisol has what effect on energy metabolism
- Gluconeogenesis (liver)
- Lipolysis (adipose tissue)
- Protein catabolism
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What effect does Leptin have on energy metabolism
- It directs storage of excess caloric intake into adipose and thus supports insulin
- Supports reproduction, erythropoiesis, and lymphopoiesis
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Incretins
Peptide hormones that augment insulin secretion 3-4 times then that of the un-augmented state
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How do Incretins work
Increases cAMP and PKA levels in beta cells increasing Ca++
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Incretin augmentation can be lost in those with
Diabetes type II
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Glucose-dependent insulinotropic polypeptide (GIP) and Glucagon-like peptide 1 (GLP1) are what
The primary hormones that act as Incretins
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Acute starvation has what net effect in the blood
- Glycogen depletion
- Increase in plasma free fatty acids
- Increase in Ketones
- Negative N2 balance (protein loss)
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Stress and Exercise has what net metabolic effect
- Decrease in Triglyceride synthesis
- Increase in Glycogenolysis, Gluconeogenesis and Lypolysis
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What are the physical signs of Hypoglycemia
- Head issues (headache, confusion, tiredness)
- Speech issues
- Heart issues (tachycardia)
- Hunger
- Hands cold, sweating, and trembling
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What are the two types on Diabetes Mellitus
- Type 1 - Impaired insulin production due to damage to Beta cells
- Type 2 - Inadequate action of insulin on insulin receptors
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What are some important signs of Diabetes Mellitus
- Plasma Glucose above 125mg/dL
- Glucosuria and Polyuria
- Acetone Breath
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What happens to the metabolism of carbohydrates in insulin deficiency
- Decrease in Glucose uptake and Glycogenesis
- Increase in Gluconeogenesis and Glycogenolysis
- This causes Hyperglycemia, Glucosuria, Polyuria, Dehydration, and eventual circulatory collapse
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What is the effect of insulin deficiency on Lipid metabolism
- Decrease in Lipogenesis
- Increase in Lipolysis
- Causing Hyperlipidemia, Ketogenesis, Ketonemia, Ketouria, Metabolic acidosis
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What is the effect of insulin deficiency on protein metabolism
- Decrease in amino acid uptake and protein synthesis
- Increase in protein degredation
- Causing Aminoacidemia, increase in nitrogen excretion, and (-) nitrogen balance
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