Flashcards in Lecture 58 Deck (37)
What are catabolic factors (hormones) that increase plasma glucose levels?
4) Growth hormone
What are anabolic factors (hormones) that reduce plasma glucose levels?
As blood glucose levels decrease, list the order of factors that occur in the body to try maintain blood glucose levels
1) Insulin production decreases (above 80 mg/dL)
2) Epinephrine and glucagon production increases (60-70 mg/dL)
3) Growth hormone production increases (60-70 mg/dL)
4) Cortisol production increases (60-70 mg/dL)
5) Adrenergic symptoms begin (anxiety, palpitation, tremor, sweating) (Just below 60 mg/dL)
6) Neuroglycopenia symptoms begin (headache, confusion, slurred speech, seizures, coma, & death) (50 mg/dL or below)
What blood glucose levels are indicative of diabetes?
1) Fasting blood glucose levels =>126mg/dL
2) Random blood glucose levels =>200 mg/dL
What is a key concept between the ratio of insulin & glucagon?
Ratios of insulin & other hormones, particularly glucagon, regulate tissue specific metabolism under different nutritional states (e.g., fed, fasting, & prolonged starvation)
What must excess glucose, amino acids, & triglycerides be converted to?
Glycogen, fat, & protein
What part of the body produces insulin in the presence of excess glucose & amino acids?
Insulin is produced by beta cells in the islets of Langerhans in the pancreas
How low must your blood glucose levels be they begin producing catabolic factors such as glucagon, epinephrine, cortisol, & growth hormone?
Below 18mg/dL or 1mmol/L
How high must your blood glucose levels be they begin producing the anabolic factor insulin?
Above 162 mg/dL or 9 mmol/L
What occurs in an insulin-activated liver?
1) GLUT2 transporters transport glucose from the gut into the liver
2) High Km (low affinity) glucokinase glycolysis
3) Increased Glycogen synthesis
4) Increased Pentose phosphate pathway
5) Increased Protein synthesis
6) Increased Fatty acid and TAG synthesis
What occurs in an insulin-repressed liver?
1) Decreased gluconeogenesis (inactive pyruvate carboxylase & fructose 1,6-bisphosphatase)
2) Decreased glycogen breakdown (inactive glycogen phosphorylase)
3) Decreased fat breakdown
What occurs in activated pathways in resting skeletal muscle?
1) GLUT4 transporter transports glucose into the muscle
2) Increased glycolysis
3) Increased glycogen synthesis
4) Increased protein synthesis
What occurs in repressed pathways in resting skeletal muscle?
1) Decreased glycogen breakdown
What occurs in activated pathways in adipose tissue?
1) GLUT4 transporter brings glucose into adipocytes
2) Increased glycolysis (PFK, pyruvate DH)
3) Increased Pentose phosphate pathway
4) Most fat stored from diet in the form of triacylglycerol
What occurs in repressed pathways in adipose tissue?
1) Decreased glycogen breakdown
How does the brain produce energy?
1) When the brain receives glucose, it uses only glucose
2) Brain completely oxidizes glucose to CO2 & H2O
Describe what occurs after excess caloric intake
1) Dietary carbohydrate and dietary protein can be converted to body fat: When caloric intake exceeds energy expenditure, dietary carbohydrate and protein can be converted to tracylglycerol in the liver for ultimate deposition in the adipose tissue
2) Dietary fat can be converted to body fat: When caloric intake exceeds energy expenditure, dietary fat can be converted to triacylglycerol in the adipose tissue
3) Insulin is an anabolic signal that promotes synthesis of glycogen, protein, & triacylglycerol
What is the basic concept of how a hormone receptor is structured and functions?
1) Exquisitely selective extracellular domain, aka ligand binding domain (LBD)
2) Hydrophobic transmembrane domain anchors receptor in membrane and couples LBD to intracellular domain
3) Cytoplasmic/intracellular domain is the effector domain
What occurs when a Receptor Tyrosine Kinase (RTK) is activated by a molecule such as insulin?
1) Insulin (in the form of a dimer) activates a Receptor Tyrosine Kinase (RTK) on responding cells
2) Tyrosine residues on the receptor become phosphorylated very rapidly
3) The enzyme and substrate are both part of the receptor (intrinsic activity)
4) Intracellular signaling proteins can now bind to the phosphorylated tyrosines and relay the signal
What are roles of Receptor tyrosine kinases (RTK)?
1) Carbohydrate utilization and protein synthesis (e.g. insulin)
2) Regulation of cell growth & survival (e.g. EGF, IGFs)
3) Angiogenesis (e.g. Vascular endothelial growth factor, VEGF)
How do the adaptor proteins bound to the phosphorylated tyrosine receptor relay the signal?
1) Adapter proteins activate Monomeric G Proteins (e.g. Ras) that activate kinases
2) Kinases that are activated include Kinase 1 (MAPKKK (RAF)), Kinase 2 (MAPKK (MEK)), & Kinase 3 (MAPK (ERK))
3) There are then changes in protein activity & gene expression
Other than RTK, what are other important hormone receptors with intrinsic enzyme activity?
1) TGF Beta receptors – serine kinases, e.g. activin, inhibin, transforming growth factor (TGF) beta, bone morphogenetic proteins (BMPs)
2) Receptor guanylyl cyclases generate the 2nd messenger cGMP, e.g. atrial natriuretic factor (ANF) & related peptide hormones
3) Again, intrinsic means the enzyme is part of the receptor protein
What is occurring in the liver when someone is hungry?
1) Increased glycogen breakdown
2) Increased gluconeogenesis
3) Increased Fatty acid oxidation
4) Increased ketone body synthesis
What occurs in an adipocyte when someone is hungry?
1) Increased triacylglycerol degradation
2) Increased fatty acid & glycerol release
3) Decreased fatty acid uptake
What occurs in muscles when someone is hungry?
1) Fuel switches from glucose to FAs & KBs
2) Protein breakdown provides AAs for liver GNG
What happens in the brain when someone is hungry?
1) Initially, glucose from the liver is formed from gluconeogenesis
2) After 2-3 weeks, uses ketone bodies
What are the two priorities during hunger?
1) Blood glucose is maintained first by degradation of liver glycogen, followed by hepatic gluconeogenesis (feed the glucose-requiring tissues)
2) Mobilization of triacylglycerols from adipose provides fatty acids & precursors for ketone bodies (feed the nonglucose-requiring tissues)
How much glucose is produced by gluconeogenesis in the kidney during an overnight fast as compared to in starvation?
1) 10% in overnight fast
2) 40% in starvation
Contrast starvation & Diabetes Mellitus (DM):
1) Slightly lowered glucose levels
2) Increased fatty acid oxidation, increased formation of ketone bodies, decreased protein synthesis in muscle and increased gluconeogenesis in liver
3) Low insulin levels
4) Increased hunger
1) High glucose levels
2) Increased fatty acid oxidation, increased formation of ketone bodies, decreased protein synthesis in muscle & increased gluconeogenesis in liver
3) Absent or normal/high insulin levels depending on type
4) Increased hunger, frequent urination, and increased thirst, (polyphagia, polyuria, & polydipsia)
What occurs in Type 1 diabetes?
1) Absolute deficiency of insulin
2) Autoimmune destruction of beta cells
What occurs in Type 2 diabetes?
1) Decreased response to insulin
3) Less glycogenesis
4) More gluconeogenesis
5) Less muscle & fat glucose uptake
6) Residual insulin restrains
What can increase your risk of developing diabetes type 2?
Metabolic syndrome (not really used clinically anymore):
1) Central or abdominal obesity
2) High fasting blood triglycerides
3) Lower blood HDL cholesterol
4) High blood pressure
5) High, but not diabetic, fasting glucose
What are types of defects that can cause genetic diabetes to arise (maturity onset diabetes of the young (MODY)?
1) Transcription factors that control expression of metabolism genes
2) Metabolic enzymes
3) Signaling defects
What is the function of Metformin?
1) Metformin activates AMP-Activated Protein Kinase (AMPK)
2) This promotes: Glycolysis in the liver & glucose uptake in muscle
3) This inhibits: Fatty acid synthesis & gluconeogenesis
What can be said about hemoglobin A1c in relation to glucose?
1) Hemoglobin A1c are normally 4-6% of total HbA1c
2) Hemoglobin A1c can be glycosylated by free glucose
3) Because this reaction is irreversible, blood HbA1c is not cleared until an erythrocyte is replaced
Compare and contrast diabetes 1 and 2
1) Usualy childhood or puberty, rapid onset of symptoms
2) Normal weight to wastd
3) ~10% of diagnoses
4) moderate genetic predisposition
5) Beta cells destroyed, no insulin produced
6) Ketosis common
7) Acute complication: Ketoacidosis
8) Treatment: insulin replacement
1) Often after age 35, gradual onset of symptoms
2) Associated with obesity
3) ~90% of diagnoses
4) very strong genetic predisposition
5) Insulin resistance with abnormal insulin levels (low, normal, high)
6) Ketosis is rare
7) Acute complication: Hyperosmolar coma
8) Treatment: Diet, exercise, oral hypoglycemic drugs, possibly insulin