Pancreas Flashcards
Human metabolic processes outside cell vs inside cell
Outside the cell:
Keep blood glucose levels within a constant range during the fed, fasted, and starved state.
- Inside the cell:
Maintain intra-cellular ATP and provide energy for high energy requiring tissues and anabolic processes
Normal fasting BG: 70-100 mg/dl
Normal BG 2h after meal:
Normal fasting BG: 70-100 mg/dl
Normal BG 2h after meal: <139 mg/dl
Blood glucose is kept within a narrow range via
Blood glucose is kept within a narrow range via tight hormonal regulation
glucose pathway after a meal
- glucose enters blood through intestine
- insulin is secreted
- glucose uptake by liver, adipose , and skeletal m.
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explain cahilll diagram based on phases
When awake, we eat approx. every 4 hours. We keep ourselves in Phase I of the Cahill Diagram.
Glucose supply between 4 – 12 hours (i.e during the last half of nocturnal sleep) comes from glucose stored as glycogen from the liver (Phase II), Glycogenolysis.
Beyond 12 hours, glucose has to be newly made by mobilizing stored energy rich substrates. This occurs mainly in the liver (Phase III), Gluconeogenesis.
The main hormone regulating metabolism during fasting is
The main hormone regulating metabolism during fasting is Glucagon
Main energy carriers in nutrition
Carbohydrates: approx. 4.7 kcal/g, main source of nutritional energy
50% of all calories in diet
Lipids: approx. 9 kcal/g, 20-30% or all calories in diet
Proteins: approx. 4.7 kcal/g, 20-30% of all calories in diet
Nucleotides: have potential caloric value, but do not significantly contribute to energy (ATP) production.
Ethanol: approx. 7 kcal/g
Digestive phase: Metabolism orchestrated almost entirely by
Digestive phase: Metabolism orchestrated almost entirely byinsulin.
Fating phase metabolism is regulated by
Glucagonandcatecholamines(epinephrine, norepinephrine)
what two hormones PARTIALLY contribute to fasting phase/
Growth hormone and cortisol also contribute somewhat to fasting-phase metabolism.
alphas and beta cells of pancreas
Beta cells produce insulin which induces uptake of blood glucose
Alpha cells produce glucagon (counter-regulation) which induces gluconeogenesis and glycogenolysis, leading to secretion of glucose and increase blood glucose
delta cells of pancreas
Delta cells produce somatostatin which inhibits the influx of glucose and amino acids; and decrease gastric secretion
insulin action in the liver
Insulin action promotes nutrient storage.
In the liver.
Insulin signaling through Akt2 activates glycogen synthase
decreases the transcription of gluconeogenic enzymes via inactivation of FOXO1.
Insulin effect on skeletal muscle,
In skeletal muscle, insulin activates glucose uptake and glycogen synthesis.
Skeletal muscle will also take up FAs for oxidation.
insulin effect on adipose tissue
In adipose tissue, insulin inhibits lipolysis & promotes glucose uptake.
type of glucose transpoters for skeletal muscle, adipose and liver
skel m and adipose are GLUT4- Need insulin to stimulate
liver is GLUT 2 which is on cell surface always taking in glucose
Blood Perfusion of the Pancreatic Islets
A
B
D
75%
20%
5%
Regulation of Insulin : β Cell Insulin Release PATHWAY
- entry of glucose into cell by GLUT 2
- Glucose is phosphorylated by glucokinase G6P
- metabolism of G6P by glycolysis, TCA and ox. phos
- K channel closes
- Depolarization of the cell6
- Ca influx in cell’
- GLP-1 Glucagon like peptide - induced PKA activates EXOCYTOSIS OF INSULIN
Primary and secondary signals for insulin secretion
The main stimulus for beta cell secretion of insulin is elevated plasma glucose
Plasma amino acids as well as the elevation of parasympathetic activity and G.I. tract hormones, secondary to food intake, serve as secondary stimuli
AkT role in mechanism of insulin
- translocate GLUT4 for glucose import
AND - INHIBIT FOX01- stop gluconeogenesis and VLDL Export
insulin inhibits
GLYCOGEN BREAKDOWN
LIPOLYSIS (FAT BREAKDOWN)
PROTEIN BREAKDOWN
glucagon inhibits
LIPID SYNTHESIS
PROTEIN SYNTHESIS
GLYCOGEN SYNTHESIS
DNA SYNTHESIS
type 1 vs type 2 hyperglycemia
1) Type 1 which is secondary to low insulin secretion (autoimmune disease destruction of pancreatic beta cells),
(2) Type 2 which is associated with target tissue resistance to insulin (receptor or post-receptor defects)
DM complications :Acute vs chronic
Acute (ketoacidosis & tissue dehydration)
Chronic (cardiovascular disease, blindness, renal failure, peripheral neuropathy, and impaired wound healing
hypoglycemia
Caused by excess insulin, failure of the glucose counter-regulatory system or drugs
types of symptoms of hypoglycemia
Neurogenic (autonomic)
Includes sweaty, hungry, tingling, shaky/tremelous, heart pounding or nervous/anxious feelings
Neuroglycopenic
Includes warm, weak, difficulty thinking/confused, tried/drowsy, faint, dizzy, difficulty speaking, blurred vision
3) Maturity-onset Diabetes of the Young (MODY)
3) Maturity-onset Diabetes of the Young 3) Maturity-onset Diabetes of the Young (MODY) which is associated with defective insulin secretion by the pancreas (MODY) w
hypoglycemia symptoms
Neurogenic (autonomic)
Includes sweaty, hungry, tingling, shaky/tremelous, heart pounding or nervous/anxious feelings
Neuroglycopenic
Includes warm, weak, difficulty thinking/confused, tried/drowsy, faint, dizzy, difficulty speaking, blurred vision
type 1 symptoms
May present as chronic fasted state, “melting flesh”, ketosis, acidosis, glucosurea, diuresis & coma
