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Nutrients and Metabolic Health > Glucose Regulation in the Peripheral Tissues > Flashcards

Glucose Regulation in the Peripheral Tissues Flashcards

1
Q

EFFECT OF INSULIN IN THE PERIPHERY
primary insulin target tissues are where

A

skeletal muscle, liver, and adipose tissue

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2
Q

role of the pancreas
what does insulin secrete/produce

A

digestive enzymes
produces primary messengers (hormones)

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3
Q

EFFECT OF INSULIN IN THE PERIPHERY
primary insulin target tissues are skeletal muscle, liver, and adipose tissue, in which the hormone modulates _______ of intracellular proteins

A

phosphorylation (within minutes)

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4
Q

EFFECT OF INSULIN IN THE PERIPHERY
primary insulin target tissues are skeletal muscle, liver, and adipose tissue, in which the hormone modulates phosphorylation of intracellular proteins(within minutes) and affects gene transcription and protein synthesis (timeframe?)

A

hours

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5
Q

PKB is activated following a cascade from what

A

insulin binding

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6
Q

when insulin activates PKB, what protein is activated

A

mTOR

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7
Q

insulin activates PKB through a series of _____ events

A

phosphorylation

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8
Q

PKB promotes glucose uptake by cells through _________ of GLUT4 transporters to the cell membrane

A

translocation

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9
Q

by enhancing GLUT4 translocation, PKB promotes increased ________ _____ by cells

A

increased glucose uptake

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10
Q

PKB promotes _____ synthesis in the liver and muscle, contributing to glucose storage

A

glycogen

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11
Q

what are the effects of insulin on muscle?

A

insulin promotes uptake of glucose by muscle for immediate use during exercise or storage as glucagon

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12
Q

how does insulin influence the liver

A

insulin stimulates the uptake of glucose by the liver, ->storage as glycogen
insulin inhibits glycogen phosphorylase, activates glycogen synthase, and prevents glucose synthesis
excess glucose in converted to fatty acids under the influence of insuiln

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13
Q

what role does insulin play in adipose tissue
insulin ______ the uptake of glucose by adipose tissue, facilitating its conversion to _____ for fat production

A

promotes
glycerol

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14
Q

what role does insulin play in adipose tissue
insulin ______ lipolysis which is the breakdown of ______ in adipose tissue

A

inhibits
triglycerides

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15
Q

MUSCLE’S ROLE IN GLUCOSE UPTAKE
What percentage of whole-body insulin-stimulated glucose uptake is accounted for by skeletal muscle

A

skeletal muscle accounts for 60-70% of whole-body insulin-stimulated glucose uptake

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16
Q

SIGNIFICANCE OF MUSCLE IN INSULIN RESISTANCE
why is muscle considered a major site of insulin in obesity and T2DM

A

muscle is a significant site of insulin resistance, making it a therapeutic target especially in obesity and T2DM

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17
Q

EFFECTS OF MUSCLE SPECIFIC INSULIN RECEPTOR KO
What were the consequence of muscle-specific KO of the insulin receptor (IR) mice

A

muscle specific knockout of IR led to increased fat mass, elevated serum triglyceride levels, and muscle insulin resistance in mice -> no significant effects on global glucose tolerance

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18
Q

impaired glucose uptake in IRS1 and IRS2 mice
what happens to glucose uptake in mice lacking both IRS1 and IRS2 in skeletal and cardiac muscle

A

mice lackibg both IRS1 and IRS2 in skeletal and cardiac muscle experience impaired glucose uptake, although without hyperglycaemia and hyperinsulineamia

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19
Q

REGULATION OF HGP BY INSULIN AND GLUCAGON
how does insulin regulate HGP in relation to glucagon

A

insulin regulates HGP by inhibiting glucagon secretion from pancreatic alpha cells

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20
Q

INSULIN’S EFFECT ON HEPATIC GLUCOSE PRODUCTION
how does insulinsuppress hepatic glucose prodcution

A

Insulin suppresses HGP by inhibiting gluconeogenic enzymes and activating glycolytic and fatty acid synthetic enzymes, resulting in the switch from fatty acid oxidation to synthesis

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21
Q

ROLE OF INSULIN IN CENTRAL SIGNALLING
What is the role of central insulin i hepatic IL-6-STAT3 signalling

A

Central insulin activates hepatic IL-6-STAT3 signaling through the brain liver axis

22
Q

CONSEQUENCES OF LIVER-SPECIFIC IR KNOWCKOUT
what are the metabolic consequences of liver specific insulin receptor KO min mice

A

LIRKO are hyperglycaemic and hyperinsulinmemic and displayed reduced liver size compared to WT mice

23
Q

INSULIN RESISTANCE IN LIVER-SPECIFIC IRS1 AND IRS2 KOs
How do liver specific IRS1KO mice and liver specific IRS2 KO mice differ in terms of insulin resistance

A

LIRS1-KO mice show insulin resistance after re-feeding but not during fasting, while LIRS2 KO mice display insulin resistance during fasting but not after re-feeding

24
Q

CONSEQUENCES OF DUAL IRS1 AND IRS2 KO IN THE LIVER
What are the consequences of liver-specific KO of both IRS1 and IRS2

A

Liver specific KO of both IRS1 and IRS2 leads to severe glucose intolerance and impaired lipid metabolism

25
Q

Role of Adipose Tissue Expansion
what effects does adipose tissue expansion have on preventing ectopic deposition of lipids in other organs

A

Adipose tissue expansion exerts a buffering effects, preventing lipids from being ectopically deposited in other organs such as the liver , muscle and pancreas

26
Q

Relationship Between Diet-Induced Obesity and Insulin Resistance
What remains the cause of insulin resistance under conditions of excess nutrition

A

diet-induced obesity remains the cause of insulin resistance under conditions of excess nutrition

27
Q

Insulin’s Effect on Glucose Uptake in Adipocytes
How does insulin stimulate glucose uptake in adipocytes, and what is the converted form of glucose

A

Insulin stimulates glucose uptake in adipocytes, where it converts into lipids as a more efficient energy storage

28
Q

Insulin’s Role in Lipolysis Inhibition
what is the effect of insulin on lipolysis, and what does lipolysis involve

A

insulin inhibits lipolysis, which is the breakdown of truglcyerides into glycerol and free fatty acids

29
Q

Impairments in Adipose Tissue of Type 2 Diabete
what changes are observed in the tyrosine phosphorylation of IRS1 and PI3K activation in the adipose tissue of T2DM

A

tyrosine phsophorylation of IRS1 and activation of PI3K are decreased in adipose tissue of type 2 diabetes

30
Q

Consequences of Fat-Specific Deletion of Insulin Receptor (IR)
What are the consequences of fat-specific deletion of IR in terms of fat mass, obesity protection and glucose tolerance

A

Fat-specific deletion of IR reduces fat mass, protects against obesity and guards against obesity-related glucose tolerance, thereby increasing longevity

31
Q

Impact of Fat-Specific Deletion of GLUT4
What happens when GLUT4 is specifically deleted in fat tissue concerning insulin-stimulated glucose uptake and insulin-mediated suppression of HGP

A

fat specific deletion of GLU4 results in decreases in insulin-stimulated glucose uptake in fat and muscle, along with impairment in insulin-mediated suppression of HGP

32
Q

Carbohydrate (CHO) Regulation of Gene Expression
how does glucose regulate gene expression, and what s the name of the transcription factor involved

A

Glucose acts via ChoRF (Transcription Factors) which binds to ChoRE on glucose responsive genes
examples may include PDX-1 and C/EBP

33
Q

Lipid Regulation of Gene Expression
how do polyunsatureted fatty acids (PUFA) contribute to transcriptional regulation and what are the key players in this process

A

Polyunsatureted fatty acids (PUFA) contribute to normal transcriptional regulation via PPARs (peroxisome proliferator)

34
Q

Cholesterol’s Role in Gene Expression
how is cholesterol involved in the regulation of gene expression, and which regulatory element is key in this process

A

Cholesterol is involved in gene expression regulation via SREBP (sterol regulatory element BP)

35
Q

Amino Acids’ Impact on Gene Expression
WHat are the various effects of amino acods on gene expression, including the aspects they influence

A

amino acids can impact transcription, ribosomes, signalling, and amino acids transport

36
Q

Glucose Regulation of Lipogenic Genes
How does glucose regulate lipogenic genes, and what is the role of ChoRE in this process

A

Glucose can regulate lipogenic genes by having ChoRE ( Carbohydrate Response Element) identified on the promoters of these genes. ChREBP binds to the CHoRE, promoting the transcription of these lipogenic genes

37
Q

Regulatory Sequences of L-type Pyruvate Kinase and S Genes
what sequences are present in ChoREs (carbohydrate response elements) and why is the correct spacing of these elements crucial fopr the transcriptional response to carbohydrate

A

ChoREs contain two E-box sequence motifs, and the correct spacing of these elements is critical for the carbohydrate control of gene transcription

38
Q

ChREBP (ChoRF) Characteristics
WHat are the key charcteristics of ChREBP

A

ChREBP is a large protein, 864 amino acids long, mainly expressed in the liver, kidney, white adipose tissue and brown adipose tissue, it contains domains suc as NLS, poly-proline doamins, basic helix loop -helic leucine zipper domain and a leucine zipper like domain.
Additionally it has potential phosphorylation sites for PKA (P1, P2 adnd P3) and a putative AMPK phosphorylation site (p4)

39
Q

ChREBP Localization and Activation
describe the cellular localisation of ChREBP in the presence of low and high glucose

A

low glucose -> ChREBP is located in the cytosol, when blood glucose increases, it translocates to the nucleus

40
Q

ChREBP-Mlx Heterodimeric Complex
How does ChREBP function, and what is its interaction with another transcription factor

A

ChREBP functions in a heterodimeric complex with another transcription factor knows as MAx-like protein X (Mlx)

41
Q

Phosphorylation State and Nuclear Localization of ChREBP
What is the role of Ser196 phosphorylation in the localisation of ChREBP, and how does its dephosphorylation affect its function

A

Ser196 phosphorylation retains ChREBP in the cytosol, but dephosphorylation, along with dephosphorylation of Ser626, and Thr666, results in nuclear localisation and binding to DNA

42
Q

Activation of Protein Phosphatase 2A (PP2A)
How is protein phosphatase 2A (PP2A) activated and what is its role in ChREBP dephosphorylation

A

PP2A is activated by xylulose 5-phopshate, a metabolote generated by the pentose phopshate pathway under high glucose conditions. It dephosphorylates Ser196, Ser626, and Thr666 of ChREBP

43
Q

ChREBP Synergy with SREBP-1c
what is the synergy between ChREBP abd Sterol Regulatory Element binding protein - 1c (SREBP-1c)

A

ChREBP acts in synergy with SREBP-1c a major mediator of insulin action on hepatic glucokinase (GK) and lipogenic genes

44
Q

Induction of Lipogenic Genes by High Carbohydrate Diet
how does insulin and glucose contribute to the induction of lipogenic genes in the liver during a high carbohydrate diet

A

(1)Insulin acts on hepatocyte insulin receptors (inc SREBP-1c) which binds to the promoter region of lipogenic enzyme genes to stimulate transcription
(2)Simultaneously, increased glucose elevates glycolysis, activating ChoRF/ ChoRF binds to a distinct site from SREBP-1c on the promoter regions of many lipogenic enzyme genes to activate their expression. ChoRF may function synergestically with SREBP to promote lipogenesis in the liver

45
Q

ChoRF/GRBP and Glucose Response
What is the role of ChoRF (glucose response binding protein) in response to glucose, and what signalling molecule is associated with it?

A

ChoRF/GRBP is involved in glucose response, potentially using glucose-6-phosphate as a signalling molecule

46
Q

Response to Glucose Deprivation
How is the response to glucose deprivation regulated, and what are the nutrient sensing response elements (NSRE) 1 and 2

A

many genes regulated by glucose, requiring insulin, are involved in the response to glucose deprivation. NSRE 1 and 2 are necessary for gene activation, with C/EBPbeta binding to the NSRE-1 sequence

47
Q

Role of PGC-1α in Gluconeogenic Enzymes
What is the role of PGC-1α in the transcription of gluconeogenic enzymes, and how is it induced?

A

PGC-1α, a transcriptional coactivator is induced in the fasted liver and by cAMP (possibly glucagon) and gluccocorticoids. It overexpresses gluconeogenic enzymes and coactivated gluccorticoid receptor and HNF-4alpha

48
Q

Role of PGC-1 in Gluconeogenesis
what is the key role of PGC-1 in regulating gluconeogensis, and which transcription fcator does it work with

A

PGC-1 is a key regulator of gluconeorgenesis, working with transcription factors such as N+HNF-4 to induce gluconeogenic genes, for example PEPCK

49
Q

Regulation of Glucose Production by Glucagon and Insulin
How does glucagon and insulin regulate glucose production in the liver through PGC-1

A

glucagon activates the cAMP pathway, leading to increased glucose production via PGC-1 expression. INsulin counteracts gluconeogenesis by inhibiting the expression such as PEPCK, potentially by blocking PGC-1 expression

50
Q

Activation of Gluconeogenic Gene Expression by Glucocorticoids
what is the role of glucocorticoids, along with PGC-1 in the activation of gluconeogenic gene expression

A

Glucocorticoids, in conjunction with PGC-1 activate the expression of gluconeogenic genes

51
Q

CREB Co-activators in Gluconeogenesis
Name the co-activators of CREB involved in gluconeogenesis

A

CREB co-activators include CREB binding protein (CBP) and TORC2 (transducer of regulated CREB activities)

Nutrients and Metabolic Health (5 decks)

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