Energy Balance/Metabolism (Day 2) Flashcards
What is the primary control mechanism of metabolism?
endocrine system
Endocrine cells in ____ secrete _____ and ____
pancreas
insulin and glucagon
a-cells: secrete glucagon
b-cells: secrete insulin
What happens to insulin during a meal?
Fasting: decreased glucose, decreased insulin, increased glucagon
Fed: increased glucose, increased insulin, decreased glucagon
What happens during the anabolic state?
Fed state: INSULIN dominates
Increased: glucose uptake glycogenesis glycolysis lipogenesis TG storage protein synthesis
Decreased: BG glycogenolysis gluconeogenesis FA oxidation TG hydrolysis protein catabolism ureogenesis ketogenesis
What happens during the catabolic state?
Fasting/starving state: GLUCAGON dominates
Increased: BG glycogenolysis gluconeogenesis FA oxidation TG hydrolysis protein catabolism ureogenesis ketogenesis
What stimulates insulin release?
- increased plasma glucose
- increased plasma AAs
- incretin release from SI (in response to CHO coming in)
- parasympathetic, vaguely-mediated reflexes originating in liver
What inhibits release of insulin?
- sympathetic stimulation: norepinephrine (ex. fight or flight)
- stress: epinephrine, cortisol from adrenal gland (fasting = form of stress)
Cellular mechanisms of insulin action
- insulin binds to receptor w/tyrosine kinase activity
- phosphorylation-mediated activation of IRSs
- coupled to diverse array of signal transduction cascades
- increased glucose uptake/utilization, increase expression of anabolic genes
How does insulin activate glucose uptake?
by inducing translocation of GLUT4 to cell membrane
What stimulated glucagon release?
- decreased plasma glucose
- increased plasma AAs (ex. if dietary protein increases, but dietary glucose decreases)
- increased sympathetic activity
- increased epinephrines release from adrenal
What inhibits glucagon release?
- increased plasma glucose
- increased parasympathetic activity
- increased plasma insulin
Cellular mechanisms of glucagon action
Receptor couple to GTP binding protein
- activated AC produces cAMP
- cAMP produces PK (protein kinase)
- PK phosphorylates P’ase kinase (activation) and glycogen synthase (inactivation)
- P’ase kinase phosphorylates glycogen phosphorylase (activation
Diabetes
dysfunctional hormonal control of metabolism
–> characterized by a chronic, persistent catabolic state (body thinks it’s starving)
Hyperglycemia due to inadequate insulin secretion, decreased response to insulin, or both
How do we Dx diabetes?
Measure:
- fasting levels of glucose in plasma
- kinetics of glucose removal after defined oral glucose load –> glucose tolerance test
Gut Microglora
largest population of microbes in body
-play a regulatory role in metabolic/immune pathways: interactive host-microbiota metabolic, signaling, immune-inflammatory axes connecting gut/liver/muscle/brain
How do artificial sweeteners affect glucose?
they induce glucose intolerance by altering gut microbiota
Diabetes Type 1
• formerly called juvenile-onset diabetes
• most severe form
• failure of pancreatic β-cells to produce/release insulin
• Incompletely understood autoimmune destruction of β-cells,
associated with genetic and/or environmental factors
• treatment: exogenous administration of insulin—resolves gluco-
regulation, but other complications (e.g. peripheral vascular disease) persist
Diabetes Type 2
• formerly adult-onset diabetes, now insulin-resistant diabetes
• accounts for about 90% of cases of diabetes worldwide
• precise cause uncertain, but is associated with obesity-induced inflammation
• progressive: insulin resistance in target cells –> compensatory
hypersecretion of insulin –> eventual loss of β-cell function
• tissues with most prominent insulin resistance: skeletal muscle, liver, adipose
Diabetes Consequences
- muscle protein breakdown
- ketoacidosis
- hyperglycermia
- increased thirst
- overeating
- glucosuria
- dehydration
- microvascular disease
- macrovascular disease
- myocardial dysfunction
Insulin resistance –> T2D
partly a response to obesity-induced inflammation originating from adipose tissue under conditions of increasing fat content
Obesity-induced inflammation compromises…
compromises insulin-dependent processes throughout body
Obesity/insulin-resistance can produce…
can produce significant derangements in body lipid/lipoprotein metabolism –> CV disease or athlersclerosis
What is a lipoprotein?
Large complex of lipid and proteins which serve as the transport vehicles for lipids (TG, cholesterol, cholesterlyl esters)
- chylomicrons
- VLDL
- IDL, LDL
- HDL
Chylomicrons
produced by/released by intestine
transports dietary lipids in body - INCREASED TG
VLDL
produced by liver
transports endogenous lipids - INCREASED TG
IDL, LDL
derived from VLDL during it’s plasma passage/metabolism
transport cholesterol to periphery - INCREASED CHOLESTEROL
HDL
precursor produced by liver, picks up cholesterol from peripheral tissues, transports it to liver
“reverse cholesterol transport” - INCREASED CHOLESTEROL
Lipoprotein metabolism
healthy state depends on high HDL/low LDL
low HDL/high LDL = atherosclerosis
Dysfunctional lipoprotein metabolism can lead to atherosclerosis
Insulin resistance:
- promotes VLDL production/secretion from the liver
- decreases expression of liver LDL receptor (increased production/decreased disposal)
- -> increased VLDL in plasma = increased TG and increased LDL - decreases plasma HDL
What is athersclerosis cause by?
elevated LDL –> increased amounts taken up in artery walls
excess LDL taken up by blood vessels –. lipid deposition in arty walls –> chronic inflammation
Metabolic Syndrome
cluster of risk factors for diabetes and CV disease
