4 Flashcards

1
Q

what does hyperglycaemia cause to macrovasculature

A

atherosclerosis

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2
Q

what does hyperglycaemia cause to microvascuolature

A

kidney and nerve disease

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3
Q

is diabetes communicable

A

non

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4
Q

what causes diabetes

A

relative insulin deficiency or resistance or both

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5
Q

type I diabetes insulin production

A

very little to none

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6
Q

type II diabetes insulin production

A

muscle sand fat develop insulin resistance and insulin secreting cells don’t produce enough insulin to compensate for it.

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7
Q

prevalence in uk of diabetes in 1996

A

1.4M

in 2035 more than 5M

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8
Q

normal blood glucose range

A

3.5 to 5.5 mmol/L before meals and less than 8 after meals

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9
Q

in times of fasting how does the brain get glucose

A

by breaking down triglycerides.

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10
Q

is the pancreas an endocrine or exocrine gland

A

primarily exocrnine but the islets of langherans of the pancreas form the endocrine part.

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11
Q

what do islets of langherans produce

A
Alpha  (α) cells  producing glucagon​
account for ~30% of human islet cells* ​
	​
Beta (β) cells producing insulin ​
~ 60% of human islet cells* ​
Delta (δ) cells producing somatostatin	​
PP (or γ) cells producing pancreatic ​
polypeptide	​
​
Epsilon (ε) cells producing ghrelin	​
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12
Q

whats the structure of insulin

A

2 chains linked by 3 disulphide linkages

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13
Q

whats the effect of zinc on insulin

A

forms hexamers

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14
Q

whats the storage form of insulin

A

hexamer

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15
Q

whats the active form of insulin

A

monomeric

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16
Q

how is the production of insulin controlled

A

transcription from gene
mrNA stability
mRNA trnaltion
post translational modification

17
Q

whats the ancestor of insulin

A

preproinsulin in pancreatic b cells
becomes proinsulin in ER
becomes insulin in Golgi after endopeptidase activity which cleave off c peptide from insulin

18
Q

what part of insulin makes it inactive

A

c peptide

19
Q

what molecule acts as the glucose sensor in the pancreas to release insulin

A

glucokinase

20
Q

ok now explain how insulin is released

A

At sub-stimulatory glucose concentrations, KATP channels are open. The resting membrane potential is maintained at a hyperpolarised level (~ −70 mV) ​

Increased ATP/ADP ratio results in closure of the KATP channels and membrane depolarisation​

Voltage-gated Ca2+ channels open, intracellular concentration of Ca2+ increases and this triggers insulin secretion ​

21
Q

what triggers insulin secretion

A

CA2plus increase

22
Q

what cells release insulin

A

pancreatic B cells

23
Q

how do pancreatic B cells release insulin

A

Pancreatic β cells release insulin in two phases ​

The first phase release is rapidly triggered in response to increased blood glucose levels ​

The second phase is a sustained, slow release of newly formed vesicles​

24
Q

what kind of receptor is the insulin receptor

A

tyrosine kinase enzyme linked

25
Q

how are insulin receptors activated

A

Insulin binds to the α subunits with the receptor.

conformational change activates Tyrosine kinase domain residing on the intracellular portion of the β subunits ​

The activated kinase domain autophosphorylates Tyrosine residues on the C-terminus of the receptor itself and phosphorylates Tyrosine residues within the adaptor protein insulin receptor substrate (IRS)​

26
Q

when theres no glucose around, what happens

A
insulin receptor is not activated
cytoplasm is inactive
GLUT4 are stored intracellular
glucose cannot cross membrane
glucose cannot be converted to glycogen.
27
Q

when glucose concentration increases what happens

A

insulin is secreted and binds the alpha subunit of tyrosine kinase receptor which phosphyoates its tyrosine residue on its beta subunit
activation of PIP3 leads to GLUT4 being transported to membrane so glucose can come in and can be converted to glycogen.

28
Q

whats the effect of insulin on glucose uptake in muscles and adipocytes

A

insulin stimulates glucose uptake

29
Q

whats the name of the glucose transporter

A

GLUT4

30
Q

whats the effect of insulin on glycogen synthesis in muscles

A

insulin stimulates glycogen synthesis in muscles

31
Q

what allows for activation of glycogen synthase

A

Akt further down pathywa from insulin phosphory.ates and inactivates glycogen synthase kinase (GSK)

32
Q

in adipocytes what does insulin do to lipogenesis

A

stimulates and inhibits it.

insulin inhibits HSL so triglycerides cannot be hydrolysed

33
Q

what happens to the liver with insulin

A

inhibits gluconeogenesis

enhances glucose uptake
increases glycogen synthesis
increases lipogenesis.

34
Q

other functions of insulin

A
Insulin promotes protein synthesis ​
and storage ​
​
It stimulates transport of aminoacids ​
into the cells​
Valine, leucine, isoleucine, tyrosine, phenylalanine​
​
It increases translation of mRNAs            ​
Synthesis of new proteins​
​
It inhibits catabolism of proteins   ​
It decreases aminoacids release ​
from cells (muscle)​
​
Insulin promotes K+ intracellular uptake​
35
Q

what diabetes does disruption of pancreatic B cells lead to

A

tupe i