Lecture 16--Glucose metabolism & Diabetes

Question 1

3 steps for metabolism

Answer 1

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

Question 2

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

Answer 2

AEROBIC: pyruvate moves into TCA and ETC

ANAEROBIC: pyruvate becomes LACTIC ACID

Question 3

The Citric Acid Cycle

Answer 3

(1) Pyruvate –> Acetyl CoA

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

Question 4

Electron transport chain

Answer 4

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

Question 5

What are the classes of carbohydrate?

Answer 5

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

Question 6

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

Answer 6

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)

Question 7

How much glucose does the brain need per minute?

Answer 7

~0.5mM/minute

Question 8

What does INSULIN do?

Answer 8

The HORMONE OF PLENTY

signals to cells to STORE energy

Question 9

What does GLUCAGON do?

Answer 9

the HORMONE OF FASTING

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

Question 10

Glucose is stored as

Answer 10

GLYCOGEN

Question 11

The pancreas is both an ________ & ______ gland

Answer 11

EXOCRINE

ENDOCRINE

Question 12

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

Answer 12

the ISLETS OF LANGERHANS

in which B-CELLS SYNTHESISE synthesise insulin

Question 13

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

Answer 13

75%

Question 14

Insulin synthesis/secretion

Answer 14

(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

Question 15

Factors that STIMULATE insulin secretion/synthesis

Answer 15

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

Question 16

Factors that INHIBIT insulin secretion/synthesis

Answer 16

(1) Somatostatin

(2) Sympathetics

Question 17

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

Answer 17

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)

Question 18

What happens after insulin secretion?

Answer 18

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

Question 19

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

Answer 19

60%

Question 20

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

Answer 20

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)

Question 21

The insulin receptor

Answer 21

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

Question 22

What effect does Insulin have in the liver?

Answer 22

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

NET: Decreases blood glucose, stores energy

Question 23

What is lipogenesis

Answer 23

TG formation

Question 24

What effect does insulin have in muscle?

Answer 24

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

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

Question 25

What effect does insulin have in Adipose tissue?

Answer 25

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

Question 26

Glycogenesis

Answer 26

Glycogen synthesis (liver, muscle)

Question 27

Glycogenolysis

Answer 27

breaking down glycogen to glucose 6 phosphate

Question 28

Glycolysis

Answer 28

Using glucose to make pyruvate (liver, muscle)

Question 29

Lipogenesis

Answer 29

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

Question 30

Protein Deposition

Answer 30

Building up protein from FA (liver, muscle)

Question 31

what are the GLUCOSE RECEPTORS

Answer 31

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)

Question 32

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

Answer 32

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

Question 33

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

Answer 33

GLUT 2 ....is insulin INDEPENDENT. ....is always expressed on cell membrane of the LIVER

Question 34

Diabetes = 'starvation in the midst of plenty'...why?

Answer 34

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

Question 35

What are the TYPES of diabetes?

Answer 35

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)

Question 36

What causes Type 1 diabetes

Answer 36

Insulin DEPENDENT diabetes mellitus (IDDM) **Overarching problem: ...with PRODUCTION/SYNTHESIS of insulin **Cause: -->SELECTIVE DESTRUCTION OF B-CELLS

Question 37

What causes Type 2 diabetes?

Answer 37

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

Question 38

Type 1 diabetes = caused by problems with _______. Type 2 diabetes = caused problems with _______.

Answer 38

Type 1=IDDM=caused by problems with SYNTHESIS/PRODUCTION of insulin Type 2=NIDDM=caused by problems with RESPONDING to insulin

Question 39

Insulin resistance

Answer 39

Loss of cellular response to insulin

Question 40

In type 2 diabetes often ________ insulin is secreted

Answer 40

In type 2 diabetes often MORE insulin is secreted

Question 41

Symptoms of diabetes (and causes for these symptoms)

Answer 41

(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

Question 42

Risk factors for type 2 diabetes?

Answer 42

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)

Question 43

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

Answer 43

Exercise increases muscle glucose uptake independent of insulin Exercise is linked to lower adiposity

Question 44

Link between obesity and diabetes....hormones?

Answer 44

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)

Question 45

What is the class of hormones released by adipose tissue?

Answer 45

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

Question 46

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

Answer 46

(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)