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Physiology 3003 > Lecture 16--Glucose metabolism & Diabetes > Flashcards

Lecture 16--Glucose metabolism & Diabetes Flashcards

1
Q

3 steps for metabolism

A

(1) Glycolysis
(2) Citric Acid cycle
(3) Electron Transport Chain

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2
Q

How is Pyruvate (from glycolysis) processed depending on whether aerobic or anaerobic conditions?

A

AEROBIC: pyruvate moves into TCA and ETC

ANAEROBIC: pyruvate becomes LACTIC ACID

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3
Q

The Citric Acid Cycle

A

(1) Pyruvate –> Acetyl CoA

(2) Acetyl CoA + oxaloacetate –> citrate–>cycles through

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4
Q

Electron transport chain

A

Electron passed between the enzyme complexes and transfers the H ion from the outer –> inner membrane
Increases [H+] in inner membrane => shuttled down concentration gradient to outer membrane through ATP-synthase => generates ATP

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5
Q

What are the classes of carbohydrate?

A

(1) MONOSACCHARIDE
(2) DISACCHARIDE
(3) OLIGOSACCHARIDE (2-10 monosaccharides)
(4) POLYSACCHARIDE (10+ monosaccharides)

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6
Q

An energy dilemma: we have a ______ supply of macronutrients. Our cells need a ______ supply of energy.

A

PULSATILE supply of macronutrients (because we eat relatively infrequently)

Our cells need a CONSTANT supply of energy
(especially the brain, exclusively glucose…0.5mM/minute)

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7
Q

How much glucose does the brain need per minute?

A

~0.5mM/minute

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8
Q

What does INSULIN do?

A

The HORMONE OF PLENTY

signals to cells to STORE energy

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9
Q

What does GLUCAGON do?

A

the HORMONE OF FASTING

Signals cells to release stored glucose (glucose is stored as glycogen)

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10
Q

Glucose is stored as

A

GLYCOGEN

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11
Q

The pancreas is both an ________ & ______ gland

A

EXOCRINE

ENDOCRINE

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12
Q

The ENDOCRINE PANCREAS contains the __________ in which _________ cells synthesise insulin

A

the ISLETS OF LANGERHANS

in which B-CELLS SYNTHESISE synthesise insulin

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13
Q

What proportion of the islets of langerhan = the B-cells

A

75%

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14
Q

Insulin synthesis/secretion

A

(1) PRE-PROINSULIN (B, C, A peptides/components/segments)

=cleavage=>

(2) PROINSULIN

=proteases cleave out the C peptide=>

(3) INSULIN (A&B peptides are joined together by disulphide bridges) + C-PEPTIDE
(4) Packaged into secretory granules

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15
Q

Factors that STIMULATE insulin secretion/synthesis

A

(1) Increase [Glucose] ++++++++++
(2) Increase [Amino Acids] ++(esp alanine)
(3) Increase [Glucagon] ++(homeostatic mechanism)

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16
Q

Factors that INHIBIT insulin secretion/synthesis

A

(1) Somatostatin

(2) Sympathetics

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17
Q

How does an increase in ECF [glucose] trigger insulin secretion?

A

Glucose enters B-cell via GLUT2 transporter=> ATP synthesis => causes K+(ATP) channels t close => depolarisation => voltage-gated Ca2+ channels open => influx Ca2+ => Triggers vesicle release => secretion insulin (+C-peptide)

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18
Q

What happens after insulin secretion?

A

Pancreas drains to the PORTAL VEIN which travels straight to through the liver

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19
Q

What ___% of insulin is cleared in the 1st pass of the liver?

A

60%

20
Q

Why are circulating insulin levels not truly indicative of insulin secretion? What is a better measurement of insulin secretion?

A

Insulin is secreted directly to portal vein and passes through the liver. 60% of insulin is cleared in 1st pass of the liver. C-peptide is a better indicator of insulin synthesis as it is synthesised in equimolar quantities to insulin)

21
Q

The insulin receptor

A

Heterotetramer (2 portions of receptor)
x2 external alpha chains
x2 internal beta chains that activate 2nd messengers (tyrosine kinase)

22
Q

What effect does Insulin have in the liver?

A

STIMULATES: glycolysis, glycogenolysis, Lipogenesis
INHIBITS: Glycogenolysis, Gluconeogenesis

NET: Decreases blood glucose, stores energy

23
Q

What is lipogenesis

A

TG formation

24
Q

What effect does insulin have in muscle?

A

STIMULATES: glycolysis, glycogenesis, Protein deposition
INHIBITS: protein degradation

NET: Decreases blood glucose, stores energy, maintains muscle mass

25
Q

What effect does insulin have in Adipose tissue?

A

STIMULATES: glycolysis

…SHUTTLES PEP & Acetyl CoA to FFA

  • -> Increase FFA uptake from VLDL via LIPOPROTEIN LIPASE expression
  • -> Reduces HORMONE SENSITIVE LIPASE (breaks down TG)

NET: reduces blood glucose, stores energy as TG

26
Q

Glycogenesis

A

Glycogen synthesis (liver, muscle)

27
Q

Glycogenolysis

A

breaking down glycogen to glucose 6 phosphate

28
Q

Glycolysis

A

Using glucose to make pyruvate (liver, muscle)

29
Q

Lipogenesis

A

Building up fat (transferring some compounds to FA) (liver, muscle, adipose)

30
Q

Protein Deposition

A

Building up protein from FA (liver, muscle)

31
Q

what are the GLUCOSE RECEPTORS

A

GLUT 2: insulin INdependent. Is always expressed on cell membrane (liver)

GLUT4: Inuslin DEPENDENT. Need binding of insulin to insulin receptor on membrane in order for transporter to be translocated to the membrane (Muscle, adipose)

32
Q

What is the insulin DEPENDENT glucose transporter? Where is it expressed?

A

Glucose transporter –GLUT 4

GLUT4: Needs binding of insulin to insulin receptor on membrane in order for transporter to be translocated to the membrane

Muscle, adipose

33
Q

What is the insulin INDEPENDENT glucose transporter? Where is it expressed?

A

GLUT 2 ….is insulin INDEPENDENT.

….is always expressed on cell membrane of the LIVER

34
Q

Diabetes = ‘starvation in the midst of plenty’…why?

A

Because pa person with diabetes can’t store blood glucose = generally THIN

35
Q

What are the TYPES of diabetes?

A

Type 1: Insulin DEPENDENT diabetes mellitus (IDDM) (early onset)

Type 2: NON-insulin dependent diabetes mellitus (NIDDM) (adult onset; associated with increased adiposity with age)

36
Q

What causes Type 1 diabetes

A

Insulin DEPENDENT diabetes mellitus (IDDM)

**Overarching problem: …with PRODUCTION/SYNTHESIS of insulin

**Cause: –>SELECTIVE DESTRUCTION OF B-CELLS

37
Q

What causes Type 2 diabetes?

A

NON-insulin dependent diabetes mellitus (NIDDM)

**Overarching Problem: … with RESPONDING to insulin
Cause: …=Loss of cellular response to insulin (insulin resistance) due to altered B-cell function

38
Q

Type 1 diabetes = caused by problems with _______.

Type 2 diabetes = caused problems with _______.

A

Type 1=IDDM=caused by problems with SYNTHESIS/PRODUCTION of insulin

Type 2=NIDDM=caused by problems with RESPONDING to insulin

39
Q

Insulin resistance

A

Loss of cellular response to insulin

40
Q

In type 2 diabetes often ________ insulin is secreted

A

In type 2 diabetes often MORE insulin is secreted

41
Q

Symptoms of diabetes (and causes for these symptoms)

A

(1) POLYURIA: ALOT of urine
(2) GLUCOSURIA: glucose is excreted in urine which gives it a sweet taste

Due to high [glucose] and kidney needs to excrete the glucose along with a lot of liquid

42
Q

Risk factors for type 2 diabetes?

A

Risk factors for NIDDM (type 2)

(1) AGE (>40years, age linked with ++adiposity)
(2) FAMILY HISTORY
(3) ETHNICITY (ethnic races=more prone)
(4) SEDENTARY LIFESTYLE (lack of exercise; exercise increases muscle glucose uptake independent of insulin!)
(5) HYPERTENSION, HYPERLIPIDAEMIA (lipid in blood)
(6) OBESITY (abdominal fat distribution)

43
Q

What is the benefit of exercise in reducing risk of NIDDM (type 2 diabetes)?

A

Exercise increases muscle glucose uptake independent of insulin

Exercise is linked to lower adiposity

44
Q

Link between obesity and diabetes….hormones?

A

Adipose tissue secretes hormones called ADIPOCYTOKINES:

(1) LEPTIN
(2) ADIPONECTIN: increases insulin sensitivity. Secretion of adiponectin is inversely proportional to TG stores…i.e. More TG (fat) in cells = less adiponectin secreted.
(3) RESISTIN: increases insulin resistance (more fat = more resistin)

45
Q

What is the class of hormones released by adipose tissue?

A

ADIPOCYTOKINES
1-Leptin
2-Adiponectin (++ insulin sensitivity, (–fat = ++ adiponectin)
3-Restin (++ insulin resistance, (++fat=++resistin secretion))

46
Q

What are the processes (8) altered by insulin secretion?

A

(1) Glycolysis (liver, muscle, adipose; ++)
(2) Gluconeogenesis (liver; –)
(3) Glycogenesis (liver, muscle; ++)
(4) Glycogenolysis (liver; –)
(5) Protein deposition (muscle; ++)
(6) Protein degradation (muscle; –)
(7) Lipogenesis (adipose; ++ Lipoprotein lipase = ++ FFA uptake)
(8) Lipolysis (adipose; – hormone sensitive lipase = – lipolysis)

Physiology 3003 (15 decks)

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