Erstellt von Marissa Alvarez
vor fast 5 Jahre
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The Endocrine Pancreas/Intermediary Metabolism
Objectives
Endocrine Control of Metabolism
____ = all chemical reactions that occur within the cells of the body
the sum of the processes in the buildup and destruction of ____; specifically: the chemical changes in living cells by which energy is provided for vital processes and activities and new material is assimilated
___ (Fuel) Metabolism - reactions involving the degradation synthesis and transformation of proteins, carbohydrates, & fats.
the intracellular process by which nutritive material is converted into ___ components
Glycogenesis = glucose to ____
Glycogenolysis = glycogen to ___
Gluconeogenesis = Amino acids to ___
Protein synthesis = AA's to ____
Protein degradation = Protein to ___
Fat synthesis (lipogenesis/triglyceride synthesis) = Fatty acids & glycerol to ____
Fat breakdown (lipolysis/triglyceride degradation) = Triglycerides to ___ & ___
Anabolism:
– Build-up of ___ organic molecules from smaller organic molecules
Catabolism
- ___ of large, energy-rich organic molecules within cells
->Excess glucose transformed to ___ and ___ to form triglycerides
->Excess a.a. transformed to glucose and fatty acids, eventually ending up as ____
ADsorptive State
(FED State)
->Carbs = ___ as major energy source (glycogen synthesis and storage)
->Excess converted and stored as ___ fat
->Fats = triglyceride ___ and storage
->Protein - protein synthesis
->Excess converted and stored as triglyceride ___
Postadsorptive State (FASTED State)
->Carbs = glycogen ___ & depletion glucose sparing for ___ use
(New glucose through ____)
->Fats = triglyceride ___ energy for non-glucose using tissues
->Protein - protein catabolism
(___ ___ for gluconeogenesis)
Tissues involved in adsorptive and post-adsorptive metabolic states:
–Liver
•Primary role in [glucose]blood maintenance
–Stores ___
–Site of _____ & other metabolic interconversions
–Adipose tissue
•Primary site of energy ___
•Regulates [fatty acid]blood
–Muscle
•Site of amino acid ___
•Major energy user
–Brain
•Can only use ___
•Cannot __ glucose
(NEED for [glucose]blood maintenance)
Other Organic Intermediaries Are Energy Sources
•Glycerol
–Backbone of triglyceride (1 glyceride + 3 Fatty acids)
–Converted to glucose by __
•Lactate
–Result of ___ glucose metabolism in muscle
–Converted to glucose by ___
•Ketone bodies (acetate acetoacidic acid β-hydroxybutyric acid)
–Produced by liver during glucose ___
•Liver cannot completely catabolize fatty acids
–Oxidation of fatty acids in liver yields ___
–Released to blood where other body cells use ketones for energy production via ___ ___ ___
•In long-term starvation:
–Brain shifts fuel metabolism to use ___
»Prevents gluconeogenesis from depleting protein
•Death due to starvation usually due to protein ___, not hypoglycemia
•High levels of ketones lead to brain use and directly inhibit protein ____
Endocrine Pancreas (Insulin and Glucagon)
______ =
Released in response to glucose and amino acids
___ digestion of nutrients, preventing excess in plasma
____ secretion of insulin, glucagon & SS itself (i.e. paracrine and autocrine actions)
INSULIN
Insulin ___ blood glucose, amino acids, and fatty acids by
–Altering transport of nutrients into cells
–Altering activity of enzymes involved in specific pathways
•Ex: ↑ glycogen synthase -> ↑ glucose to glycogen rate
•Ex: ↓ hormone-sensitive lipase -> ↓ lipolysis (conversion of triglycerides to FFA+glycerol)
Control of carbohydrates:
•Circulating glucose concentration based on balance of:
–Glucose absorption from GI tract
–Glucose transport into cells
(Only these two are subject to control)
–___ glucose production
(Only these two are subject to control)
–Urinary excretion of glucose
Glucose Transporters
1.) ___ facilitated diffusion into cell (through ___)
2.) Glucose -> glucose-6-phosphate
–Phosphorylation
»Traps glucose inside cell
»Keeps intracellular glucose concentration __
Glucose transporters
GLUT-1
Blood-brain barrier
GLUT-2
->Kidney and intestinal cells
->Na-glucose cotransporter
GLUT-3
____
GLUT-4
->Most cells of body
->ONLY transporter that is sensitive to ___
->Normally cells are relatively impermeable to glucose
->Abundant in resting ___ muscle & ___ ___
->Recruitment triggered by insulin
Insulin lowers blood glucose levels and promotes carbohydrate storage
Insulin facilitates glucose transport into cells by insertion of __ at the cell membrane.
***Brain, exercising muscle, liver are NOT dependent on ___ for glucose uptake***
-Brain = GLUT 1 and GLUT3
-Exercising = contraction-induced glut-4 insertion
-Liver = Not Glut4 dependent
Insulin actions on Fat
1. Insulin increases the transport of __ ___ and glucose (via GLUT4) into ___ cells
2. Insulin promotes reactions that use fatty acids and glucose for ___
synthesis
3. Insulin ___ lipolysis
Insulin actions on protein
1. Insulin promotes the active transport of ___ ___ from the blood into
muscles and other tissues
2. Insulin increases the rate of amino acid incorporation into protein by stimulating the cell's protein-___ machinery
3. Insulin ___ protein degradation
CONTROL OF INSULIN SECRETION
Blood glucose is primary stimulus of insulin secretion, but also by:
↑ blood amino acids
Amino acid uptake enhanced
↑ protein synthesis
Stimulates insulin via excitation-secretion coupling
Food intake:
____: glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide (GLP)
Feed-__ notification of impending rise in blood nutrients
(Stimulates insulin via cAMP -> Ca2+)
Nervous input to _-islets:
->Parasympathetic (vagal) stimulation
(ACh stimulates via IP3/Ca2+)
(Also feed-forward)
->Sympathetc inhibition & Epinephrine -> ↓cAMP
REVIEW
Abnormalities in insulin secretion
->Diabetes - “siphon” or “running through”
reference to the large volume of urine output characteristic of diabetes
1.) Diabetes Mellitus
Mellitus = ____
___glycemia - reduced cellular glucose uptake, liberation of glucose into the circulation from the liver
2. Diabetes insipidus
Insipidus = ___
->Due to lack of ___
1. Diabetes mellitus - hyperglycemia
A. Type 1 (insulin-___ or juvenile-onset)
Lack of insulin ____
~5% of all diabetes mellitus cases
Autoimmune process involving the erroneous destruction of pancreatic -> cells by activated T lymphocytes
Individuals require ___ insulin for survival
1. Diabetes mellitus - hyperglycemia
B. Type 2 (non-insulin-dependent or ___ onset)
Lack of ___ to insulin
~__ of all diabetes mellitus cases
____ is a major risk factor and can lead to inadequate insulin secretion & down-regulation of cellular insulin receptors.
90% of T2 Diabetics are overweight to obese
Gestational Diabetes
- abnormally elevated glucose levels during pregnancy as a result of decreased insulin ___ that occurs in approximately 4% of pregnancies
similar to Type _
Cause unknown, but goes ___ following delivery.
Associated with greater incidence of Type 2 diabetes ___ in life
Obesity and Type 2 Diabetes
Metabolic Syndrome (Syndrome X) – obesity, high triglycerides, low HDL, high blood glucose, high blood pressure
Adipokines:
->___ – interferes with insulin actions, increased in obesity
->____ – enhances insulin sensitivity, decreased in obesity
Inflammation – obesity is an “inflammatory state” and increases in things such as TNFα can decrease ___ to insulin
___ fatty acid levels
- accumulation in muscle can interfere with actions of insulin
- accumulation in liver can lead to increased hepatic glucose production
- can trigger apoptosis of ___ cells
Insulin Deficiency
Long-term Consequences
Diabetic Retinopathy: Vision ___
A.) Nonproliferative (most common)
Pouch formation of capillaries in the back of the eye, leaking fluid and causing the eye to be unable to focus (__ __).
B.) Proliferative (less common)
Damaged vessels completely close off and new ones form, but are weak and leak blood (__ ___).
->Scar tissue can also form causing more damage to eyesight
Neuropathy: Sensorimotor and Autonomic Neuropathy
Sensorimotor Neuropathy:
Malfunction in nerves fibers that supply sensory input, leading to ___ and/or pain occurring typically at the extremities. Due to damage of blood supply to these nerves in a ___ environment.
Autonomic Neuropathy:
Malfunction in nerve fibers that control the heart, ___ tract, and urinary function.
Common problem in diabetics is the inability to control ___ ___ and pressure to keep blood flowing normally to the brain when they stand up and as a result ___. Also due to damaged blood vessels around the nerves.
3. Diabetic Nephropathy: Kidney Failure
Destruction of the glomerular capillaries in the kidney which eventually leads to kidney failure and death; characterized by increased plasma ___ in the ___.
Treatment of Diabetes
Type 1:
Very controlled regimen of insulin ____ timed around meals
Management of the types and amounts of foods consumed
Exercise (remember that glucose uptake in exercising muscle is NOT insulin-____)
Treatment of Diabetes
Type 2:
Dietary control and exercise may be all that’s necessary
->10% weight __ can improve sensitivity to insulin significantly
Pharmacological Intervention:
Stimulation of insulin secretion by β cells (____)
Suppressing liver output of glucose (__)
Blocking enzymes that digest carbohydrates (α glycosidase inhibitors)
Increasing sensitivity to insulin (thiazolidinediones)
Mimicking the ____ (GIP, GLP)
Increasing endogenous GLP-1 (Dipeptidyl peptidase or DPP-4 inhibitors)
**If Type 2 persists, it can become __ _ due to depletion of β-cells
Insulin Excess
Consequences are primarily manifestations of the effects of ___ on the brain
Insulin Shock:
Can occur in a diabetic patient when too ___ insulin is injected
Symptoms: largely due to effects at brain
Treatment: ___ at first signs
Reactive Hypoglycemia:
beta-cell ___ or over-responsive beta-cells
Insulin secretion ___ in response to elevated blood glucose and thus too much glucose is driven into cells
Symptoms: tremor, sleepiness, inability to concentrate
Treatment: limited ___ diet
Glucose maintenance also involves α-cells of the islets
Glucagon promotes ↑ blood glucose during ____ state
Amino acid paradox (i.e. high protein meal)
↑ amino acids stimulate both α and β-cells
If ONLY insulin is stimulated -> ___
Would promote further storage of already limited carbohydrate
Parallel simulation of glucagon ensures glucose availability via hepatic glucose production
Ultimately, glucose remains normal
Abnormalities of Glucagon Secretion
There are __ __ clinical abnormalities associated with oversecretion or under secretion of glucagon
Glucagon is usually elevated during diabetes and exaggerates the issue
Insulin is necessary for glucose to enter ___ cells
Thus, glucose ___ inhibit glucagon secretion
For this reason, some Type 1 diabetics respond better to insulin in combination with ___, which inhibits ___ secretion
Other Hormones play role in glucose homeostasis
REVIEW