PSIO 303 Block 3

Which of the following is NOT a component (major or additional) of the Metabolic Syndrome?

-hyperinsulinemia

-dyslipidemia

-hypercoagulability

-heart attack and stroke

-adipocyte dysfunction

heart attack and stroke

T/F: By definition, an individual with the Metabolic Syndrome will always also develop type 2 diabetes.

False

T/F: The earliest defects that arise with Metabolic Syndrome are insulin resistance and hypertension.

False

The cheapest, reasonably accurate assessment of visceral obesity is:

Waist circumference

T/F: Adipose tissue stores lipid, but it also functions as an endocrine organ for the release of hormones and other types of chemical messengers.

True

The type of tissue primarily responsible for peripheral glucose disposal and for whole-body insulin resistance is:

Skeletal muscle

As the Metabolic Syndrome progresses towards overt type 2 diabetes, symptoms typically arise chronologically. Which of the following arrangements best represents the chronological order of their development, from earliest to latest.

Central adiposity, insulin resistance, hyperinsulinemia, retinopathy

T/F: An individual with a 2-hour glucose level of 180 mg/dl during an OGTT would be diagnosed with type 2 diabetes.

False

Which of the following are potential consequences of long-term hyperglycemia? (select all that apply)

-Oxidative stress caused by reactive nitrogen species.

-Oxidative stress caused by Advance Glycation End products (AGE).

-Kidney damage

-Eye damage

-Nerve damage

Kidney damage

Eye damage

Nerve damage

T/F: The liver is an organ with the important functions of both a) removing glucose from the bloodstream and storing it as glycogen and b) delivering glucose into the bloodstream following stimulation of glycogen breakdown.

True

Which of the following statements about the Metabolic Syndrome are TRUE (check all that apply)?

-Metabolic Syndrome is a clustering of several pathologies that increases the risk for cardiovascular disease.

-The symptoms for Metabolic Syndrome develop very rapidly.

-Metabolic Syndrome is known by several other names, including Syndrome X, the Insulin Resistance Syndrome, and the CardioMetabolic Syndrome.

-There is a greater prevalence of Metabolic Syndrome among older people.

-Increased subcutaneous adiposity is closely associated with the development of other components of Metabolic Syndrome.

Metabolic Syndrome is a clustering of several pathologies that increases the risk for cardiovascular disease.

Metabolic Syndrome is known by several other names, including Syndrome X, the Insulin Resistance Syndrome, and the CardioMetabolic Syndrome.

There is a greater prevalence of Metabolic Syndrome among older people.

The liver: (select all that apply)

-Is the first organ to process nutrients from the intestines via the hepatic-portal circulation.

-Breaks down stored glycogen to glucose in a process called gluconeogenesis.

-Produces glucose de novo from various substrates in a process known as glycogenolysis.

-Modulates gluconeogenesis and glycogenolysis in response to insulin and glucagon.

-Stores glucose in the form of glycogen.

-Is the first organ to process nutrients from the intestines via the hepatic-portal circulation.

-Modulates gluconeogenesis and glycogenolysis in response to insulin and glucagon.

-Stores glucose in the form of glycogen.

Which of the following can be detected by specific neurons in the hypothalamus and can modulate neural output from the CNS to regulate glucose metabolism? (select all that apply)

-Glucose

-Insulin

-Free fatty acids

-Reactive oxygen species

-Adipokines

-Glucose

-Insulin

-Free fatty acids

-Adipokines

T/F: The microvascular complications (e.g. retinopathy) of the Metabolic Syndrome start developing during the phase of compensatory hyperinsulinemia.

False

T/F A chemical messenger secreted by one cell and acting on an adjacent cell in the same tissue is an example of autocrine communication.

False

Which of the following statements about protein phosphorylation is/are TRUE? (select all that apply)

- It occurs only on serine, threonine, and tyrosine amino acid residues.

-It requires the addition of water.

-Phosphorylation can increase the catalytic activity of enzymes.

-Phosphorylation can decrease the catalytic activity of enzymes.

-Kinases and phosphatases alter the functions of cellular proteins via the same mechanism.

- It occurs only on serine, threonine, and tyrosine amino acid residues.

-Phosphorylation can increase the catalytic activity of enzymes.

-Phosphorylation can decrease the catalytic activity of enzymes.

T/F Phosphorylation events remain constant throughout the subsequent stages of cellular signal transduction.

False

Select all of the TRUE statements about the insulin receptor:

-The insulin receptor is a catalytic receptor.

-The insulin receptor dimerizes after insulin binding.

-The insulin receptor undergoes autophosphorylation on threonine residues when insulin binds to the receptor.

-The insulin receptor can activate adenylate cyclase upon insulin binding.

-The insulin receptor phosphorylates tyrosine residues on cytosolic effector proteins.

-The insulin receptor is a catalytic receptor.

-The insulin receptor phosphorylates tyrosine residues on cytosolic effector proteins.

T/F Adenylate cyclase (AC) is activated by Gs.

True

T/F Binding of plasma membrane receptor tyrosine kinases by ligand results in immediate maximal activation of the receptor tyrosine kinase activity.

False

List correctly the order of events associated with GPCR activation from earliest to latest event (1 through 7).

-The G-protein dissociates from the receptor.

-The alpha-subunit modulates the effector protein to change second messenger production in the cell.

-GDP is exchanged for GTP within the associated G-protein.

-The alpha-subunit of the G-protein dissociates from the beta-gamma subunit.

-Ligand binding results in receptor activation.

-GTP is hydrolyzed to GDP on the alpha subunit.

-The alpha and beta-gamma subunits of the G-protein re-assemble with each other.

-Ligand binding results in receptor activation.

-GDP is exchanged for GTP within the associated G-protein.

-The G-protein dissociates from the receptor.

-The alpha-subunit of the G-protein dissociates from the beta-gamma subunit.

-The alpha-subunit modulates the effector protein to change second messenger production in the cell.

-GTP is hydrolyzed to GDP on the alpha subunit.

-The alpha and beta-gamma subunits of the G-protein re-assemble with each other.

The Km of GLUT2 is much greater than the Km of GLUT1, which means that glucose transport via GLUT2 will saturate...?

at a higher glucose concentration than GLUT-1.

T/F Insulin can act on the smooth muscle cells in the arterioles of skeletal muscle tissue to activate nitric oxide synthase (eNOS), leading to nitric oxide (NO) production.

False

Insulin increases glucose transport into skeletal muscle cells by:

Increasing translocation of GLUT-4-containing vesicles to the plasma membrane.

The termination step of the signal transduction process can involve which of the following events:

ALL:

-Dissociation of the ligand from the hormone receptor.

Internalization of the hormone-receptor complex.

-Dephosphorylation of the activated receptor, if phosphorylation of the receptor was part of the transduction process.

Which of the following statements regarding signal transduction is FALSE?

-The phosphorylation of proteins is a critical component of signal transduction that modifies cell function.

-Signal transduction relies on chemical messengers such as ions, metabolites, and hormones.

-The use of second messengers allows for signal transduction events to be amplified inside of the cell.

-Signal transduction relies exclusively on cell surface receptors in order to change cellular behavior.

-Signal transduction is a mechanism for altering various functions of cells.

Signal transduction relies exclusively on cell surface receptors in order to change cellular behavior.

In the ß-cells of the pancreas, the process of glucose-stimulated insulin secretion involves the movement of K+ across membranes. Which receptor type would this movement require?

Ligand-gated ion channel receptor.

T/F The alteration in cell response brought about by a ligand binding to a GPCR is dependent on the specific receptor type and the G-protein expressed in a cell.

True

T/F PKA activity is increased when cAMP binds to the catalytic subunits of the enzyme and allosterically activates them.

False

Which of the following statements about ligand-gated ion channel receptors are TRUE? (select all that apply)

-They are the only plasma membrane receptor category that modifies ion flux in cells.

-They can function by either opening or closing ion channels.

-They can themselves be ion channels or can associate with physically distinct ion channels.

-They act by allowing ions to move down their concentration gradient across membranes.

-They can function by either opening or closing ion channels.

-They can themselves be ion channels or can associate with physically distinct ion channels.

-They act by allowing ions to move down their concentration gradient across membranes.

Select all of the statements about GPCRs that are FALSE:

-The alpha subunit of the G-protein is deactivated by the hydrolysis of GTP to GDP.

-The GPCR must be activated by a ligand before it can activate the G-protein.

-The alpha subunit of the G-protein functions by synthesizing GTP from GDP and Pi.

-GS can either activate or inhibit adenylate cyclase, depending on which hormone binds to the receptor that associates with GS.

-Only the activated alpha subunit of the G-protein can modulate effector proteins.

-The alpha subunit of the G-protein functions by synthesizing GTP from GDP and Pi.

-GS can either activate or inhibit adenylate cyclase, depending on which hormone binds to the receptor that associates with GS.

-Only the activated alpha subunit of the G-protein can modulate effector proteins.

In which organs in humans is the GLUT-2 glucose transporter isoform highly expressed? (select all that apply)

Intestine, Liver, Kidney.

NOT: skeletal muscle or beta cells of pancreas (rodents)

Which of the following statements about insulin receptor substrate (IRS) proteins and their function is FALSE:

-IRS proteins are phosphorylated on tyrosine residues by the activated insulin receptor.

-Tyrosine phosphorylation of IRS increases the enzymatic activity of the IRS protein.

-Tyrosine-phosphorylated IRS acts as a docking protein to regulate downstream signaling factors, such as PI3K.

-The SH2 domain is located on the target protein and is involved in the recognition of phosphorylated tyrosine on the IRS.

-Tyrosine-phosphorylated IRS can propogate signaling to modulate numerous aspects of cell metabolism, such as glucose transport, glycogen synthesis, lipid synthesis, and protein synthesis.

-Tyrosine phosphorylation of IRS increases the enzymatic activity of the IRS protein.

T/F Blood flow in the capillary beds of skeletal muscle has a significant impact on glucose removal from the blood by regulating the delivery of glucose and insulin to the skeletal muscle cells.

true

T/F The magnitude of the ultimate intracellular response initiated by ligand binding to plasma membrane receptors is linearly related to the number of these receptors bound by the ligand.

False

The "transduction" step of signaling by plasma membrane receptors involves:

The activation of the plasma membrane receptor, which then produces an initial second messenger.

T/F Phosphorylation events remain constant throughout the subsequent stages of cellular signal transduction.

False

Which of the following statements about the transport of glucose across the endothelium of capillaries in skeletal muscle is FALSE?

-The transendothelial glucose transport process can be directly increased by insulin.

-Enhanced blood flow to the capillary can increase the diffusion of glucose into the extracellular space surrounding the myocytes.

-The amount of glucose that is delivered across the endothelium to the skeletal muscle cells can influence the rate of glucose transport by the muscle cells.

-The transendothelial glucose transport process is mediated by the GLUT-4 isoform.

-The transendothelial glucose transport process can be directly increased by insulin.

-The transendothelial glucose transport process is mediated by the GLUT-4 isoform.

T/F The glucose transporter isoform highly expressed in nerve cells throughout the body is GLUT-3.

True

An inhibitor of the serine kinase GSK-3beta will have what effect on insulin-resistant skeletal muscle? (select all that apply)

-It will cause increased insulin-stimulated tyrosine phosphorylation of IRS-1.

-It will cause an increase in insulin-stimulated glucose transport activity.

Glucose delivery to skeletal muscle tissue is reduced in the Metabolic Syndrome due which of the following mechanisms: (select all that apply)

-Impaired insulin stimulation of eNOS in endothelial cells of arterioles.

-Less blood flow to the capillaries perfusing the muscle.

-Reduced NO-stimulated vasodilation of arterioles.

Serine phosphorylation of IR and IRS is known to impair the functionality of insulin signaling. Which of the following kinases can initiate this effect? (select all that apply)

JNK, p38 MAPK, GSK-3beta

Oxidative stress can lead to insulin resistance in skeletal muscle. This is associated with decreased protein expression of...

IRS

Which of the following cell types is NOT expressed in the Islet of Langerhans?

Gamma Cells

T/F Following the consumption of a meal, parasympathetic nerve activity to the pancreas is increased. This will activate Ach receptors in the Beta cells and contribute to an increase in insulin secretion.

True

T/F Based specifically on the anatomical organization of cells within pancreatic islets and the direction of systemic circulation of factors in the blood, the Alpha cells are able to exert more control locally on Beta cells than Beta cells can on Alpha cells.

False