glucose and insulin physiology (mini learning) Flashcards
(97 cards)
1
Q
What do all tissue use glucose as ?
A
Their primary source of energy
2
Q
What is different about the interaction between the CNS and glucose ?
A
CNS cannot substitute glucose, so delivery is therefore critical
3
Q
How is glucose stored ?
A
as glycogen
4
Q
Where is glycogen stored, primarily ?
A
- the liver
- muscle
5
Q
What is considered the normal
a) fasting blood-glucose range ?
a) post-prandial blood glucose range ?
A
- 4-6 mmol/L (fasting)
- 8 mmol/L (2hrs post eating/post-prandial)
6
Q
What blood glucose level is considered hyperglycaemia ?
A
>10 mmol/L (sustained)
7
Q
What blood glucose level is considered hypoglycaemia ?
A
<3 or 4 mmol/L
8
Q
How much glucose is lost via the kidneys per day ?
A
<0.3 g
9
Q
What cells secrete insulin?
A
beta cells in islets of langerhans (pancreas)
10
Q
What action does insulin have on blood glucose levels ?
A
decreases it
11
Q
Which cells secrete glucagon ?
A
glucagon = alpha cells in islets of langerhans (pancreas)
12
Q
What effect does glucagon have on blood glucose levels ?
A
glucAgon = ^ increase glucose
13
Q
What state does insulin rectify
a) hypoglycaemia ?
b) hyperglycaemia ?
A
hyperglycaemia
insulin decreases blood glucose
14
Q
What state does glucagon rectify
a) hypoglycaemia ?
b) hyperglycaemia ?
A
hypoglycaemia
glucagon increases blood glucose
15
Q
What stimulates the release of glucagon ?
A
low blood glucose levels
usually the fasting state
16
Q
What stimulates the release of insulin ?
A
high blood glucose levels
usually the post-prandial state
17
Q
Which 2 hormones are involved in the endocrine control of glucose homeostasis ?
A
- insulin
- glucagon
18
Q
What are the 3 main insulin sensitive tissues ?
A
- liver
- muscle
- fat (adipocytes)
19
Q
What are the 3 main glucagon sensitive tissues ?
A
- liver
- muscle
- fat (adipocytes)
20
Q
What are the 3 main tissues involved in glucose homeostasis ?
A
- liver
- muscle
- fat (adipocytes)
21
Q
What are levels of
a) insulin
b) glucagon
like in the fasting state ?
A
fasting
insulin = decreased
glucagon = increased
22
Q
What are levels of
a) insulin
b) glucagon
like in the post-prandial state ?
A
post-prandial
insulin = increased
glucagon = decreased
23
Q
What is the action of glucagon in the fasting state ?
A
- released from alpha cells
- acts on liver to release endogenous glucose
glucose can then travel through blood to act on necessary tissues
24
Q
What tissue is insulin independent ?
A
the brain
25
What is the action of insulin in the ‘fed’ state ?
- beta cells release insulin
- stimulates **insulin dependant tissues** (muscle and fat) to **increase glucose uptake**
- turns off endogenous glucose production in the liver (**turns off glycogenolysis**)
26
What else is involved in glucose homeostasis alongside insulin and glucagon ?
**enteroendocrine cells** in small+large intestine
27
What is the role of enteroendocrine cells in glucose homeostasis ?
- stimulated by glucose/amino acids present in intestines
- produce hormones (GLP-1)
- GLP-1 **stimulates insulin** secretion via beta cells
= **reduces blood glucose**
28
What is the main hormone that enteroendocrine cells produce in response to glucose/amino acids in the intestines ?
GLP-1
*glucagon-like-peptide-1*
29
Where GLP-1 receptors primarily located ?
on **beta cells** in islets of langerhans
30
What are the 2 main effects that GLP-1 has on the body ?
- increase insulin secretion = decrease blood glucose
- induce feeling of ‘fullness’ after a meal
31
What 2 conditions can GLP-1 agonist drugs be used to treat ?
- **diabetes** (decreasing hyperglycaemia)
- **obesity** (inducing a feeling of fullness)
32
What causes hyperglycaemia?
- impaired insulin secretion
- impaired insulin action
33
What often causes impaired insulin secretion ?
loss of functioning beta cells
*could be due to:
- autoimmune destruction in T1D
- surgery to remove pancreas
- damage to pancreas/pancreatitis
- generic mutations*
34
What often causes impaired insulin action ?
reduced insulin sensitivity
*occurs in type 2 diabetes*
35
What is the main difference between type 1 and 2 diabetes ?
Type **1** = loss of insulin **secretion** due autoimmune destruction of beta cells
Type **2** = loss of insulin **action** due to defects in release, sensing and/or signalling
36
What causes hypoglycaemia ?
- excessive glucose utilisation/loss
- excessive insulin secretion levels
- insufficient glucagon secretion levels
37
What is congenital hyperinsulinism ?
babies are born with either
- too many beta cells
- inability to switch off insulin when glucose is low
38
What are insulinomas ?
pancreatic beta cells that turn cancerous and overproduce insulin
39
What are the most common causes of hypoglycaemia in diabetes ?
- patients **overusing insulin**
- unawareness due to frequently low blood sugars causing a sense of **de-sensitisation to the symptoms**
40
What are the 2 main groups of glucose transport proteins ?
- SGLT
- GLUT
41
Which class of glucose transporters enable passive transport of glucose ?
GLUT transporters
42
Which class of glucose transporters enable Na-coupled transport (co-transport) of glucose ?
SGLT transporters
43
How do GLUT transporters work/allow glucose into cells ?
- **glucose binds** to transporter
- **changes configuration** of protein
- allows glucose to pass through freely
44
How do SGLT transporters work/allow glucose into cells ?
- Na moves through protein down Na conc gradient
- takes glucose with it into the cell
45
Are SGLT transporters
a) insulin sensitive ?
b) insulin insensitive ?
insulin **insensitive**
46
What does ‘insulin-sensitive transporter’ mean ?
the transporter **requires presence of insulin** in order to transport glucose across membrane
47
What does ‘insulin-insensitive transporter’ mean ?
the transporter **doesn’t require presence of insulin** in order to transport glucose across membrane
48
What are the 2 main SGLT proteins regarding glucose transport ? Where is each primarily found ?
- SGLT1 *(intestines)*
- SGLT2 *(proximal tubule of kidney)*
49
How many molecules of Na and glucose does a SGLT2 transporter carry at once ?
SGLT = 1:1 ratio
**= 1Na + 1glucose at a time**
50
How many molecules of Na and glucose does a SGLT1 transporter carry at once ?
SGLT 1 = 2:1 ratio
**= 2Na + 1 glucose at a time**
51
What is the affinity *(Km) * of SGLT1 for glucose ?
SGLT1 *Km* = **2mM glucose**
*this means 2mM glucose fully saturates the transporter*
52
What is the affinity *(Km) * of SGLT2 for glucose ?
SGLT2 *Km* = **5mM glucose**
*this means 5mM glucose fully saturates the transporter*
53
Which type of diabetes are SGLT2 inhibitors approved as a treatment for ?
Type 2
54
How do SGLT2 inhibitors help treat diabetes ?
**prevent reabsorption of glucose within the kidneys**, so it’s excreted from the body
55
How many transporters are there in the GLUT family ?
13
56
Which 3 GLUT transporters have the most major functional role in glucose homeostasis ?
- GLUT**1**
- GLUT**2**
- GLUT**4**
57
Which of the 3 major GLUT transporters are insulin-insensitive ?
GLUT**1+2**
58
Which GLUT transporter is mainly found in the brain ?
GLUT**1**
59
Where is the GLUT2 transporter mainly found ?
- kidney
- liver
- pancreas
60
Which GLUT transporter is involved in stimulating insulin secretion in the islets of langerhans ?
GLUT2
61
Which is the main GLUT transporters is insulin-sensitive ?
GLUT4
62
Where is GLUT4 transporter found ?
- adipose tissues (adipocytes)
- striated muscle
- heart
63
What is the affinity of GLUT1 for glucose ?
approx. **5mM**
*= conc of glucose that would fully saturate the transporter*
64
What is the affinity of GLUT4 for glucose ?
approx. **5mM**
*= conc of glucose that would fully saturate the transporter*
65
What is the affinity of GLUT2 for glucose ?
approx. **17mM**
*= conc of glucose that would fully saturate the transporter*
66
Which transport protein is used in the co-transport of glucose on the apical membrane of entericytes in the small intestine ?
SGLT**1**
*2Na + glucose into cell*
67
Which transport protein is used to transport glucose out via the basolateral membrane of entericytes in the small intestine ?
GLUT**2**
68
Which transport protein is found on erythrocytes (RBCs), allowing glucose to be transported in blood ?
GLUT**1**
69
In a healthy kidney, is most glucose excreted or re-absorbed ?
about **99% is re-absorbed**
70
Where does the re-absorption of glucose occur in the kidney ?
in 2 areas of the **proximal convoluted tubule**
71
What are the 2 parts of the proximal convoluted tubule involved in glucose re-absorption ?
- early proximal
- late proximal
72
Which glucose transport protein is found in the **early** proximal convoluted tubule ?
**early** = SGLT**2**
73
Which glucose transport protein is found in the **late** proximal convoluted tubule ?
**late** = SGLT**1**
74
Which section of the proximal convoluted tubule is responsible for the majority of glucose reabsorption ?
>90% reabsorbed in **early** tubule
75
What is the mechanism of glucose absorption in the primary convoluted tubule ?
same as in ileum = **co-transport**
- **SGLT1/SGLT2**transports Na and glucose into cell
- **GLUT1/GLUT2** transports glucose out into blood
- Na-K pump maintains conc gradient
76
Why does glucose reabsorption not work well in a person with diabetes ?
absorptive **capacity of glucose transporters is overwhelmed**
77
What does glucose in the urine result in ?
**an osmotic gradient**, pulling large amounts of water into urine
78
How does glucose stimulate insulin release from the beta cells ?
- GLUT**1+2** take glucose into beta cells
- glucose is **metabolised**, generating ATP
- **ATP closes a K channel** in the memebrane
- depolarises the cell = causes **influx of Na and Ca**
- Ca influx results in **exocytosis of insulin**
79
What are the 6 simplified steps of glucose-stimulated insulin release ?
1. uptake
2. metabolism
3. K channel closure (via ATP)
4. depolarisation
5. Ca channel open/influx
6. exocytosis/release of insulin
80
What happens in GLP-1 mediated insulin release from the beta cells ?
*GLP-1 produced when high blood glucose*
- **GLP-1 binds to receptor** on membrane
- **increases cAMP** levels in cell
- cAMP **activates PKA** (protein kinase A)
- causes **exocytosis of insulin**
81
Is insulin a growth hormone ?
yes
82
What processes is insulin involved in ?
- glucose homeostasis
- lipid metabolism
- protein metabolism
- growth
- reproduction
- cognition
83
Which metabolic pathways does insulin stimulate/up-regulate ?
- **glycolysis**
- **glycogenesis**
- **glucose uptake**
- **lipogenesis**
- **amino acid uptake**
- protein synthesis
- DNA synthesis
84
Which metabolic pathways does insulin inhibit/down-regulate ?
- **gluconeogenesis**
- **lipolysis**
- apoptosis
- autophagy (reusing old cell parts)
85
Where in the cell do most of the effects of insulin take place ?
in the cytoplasm
86
Can insulin impact gene expression ?
Yes
87
Which glucose transporter does insulin have an up-regulatory effect on the production of within cells ?
GLUT**4**
88
Is GLUT4 insulin sensitive or insensitive in the transport of glucose ?
insulin sensitive
89
How does insulin interact with GLUT4 to stimulate glucose transport into cells ?
- **insulin binds to receptor** on cell membrane
- **activates tyrosine kinase ** component of the receptor
- tyrosine kinase triggers **signalling cascade**
- results in **translocation of GLUT4 from vesicles** inside cell **into membrane**
- GLUT4 efficiency is therefore increased
90
How does metformin increase sensitivity of the body to insulin ?
acts on the insulin-GLUT4 pathway to **increase expression of GLUT4 in membrane**
*stimulates signalling cascade that results in translocation of GLUT4 into membrane*
91
What happens to blood glucose levels when there is an insulin-sensing defect ? why?
blood glucose levels rise = **hyperglycaemia**
because…
- **pathways stimulated by insulin are not responding** (e.g glycogenesis) so glucose isn’t being removed
- **pathways inhibited by insulin aren’t responding** (e.g gluconeogenesis) so more glucose is being created and released
92
What are the short-term complications of hyperglycaemia ?
- **glucosuria** (glucose in urine)
- **polyuria** (more urine production)
- **dehydration**
- **ketoacidosis**
93
What are the long-term complications of hyperglycaemia ?
**glucotoxicity** in neural cells/capillary endothelial cells manifesting as…
- **peripheral vascular disease**
- **peripheral neuropathy**
- **kidney disease**
94
What does the body do to compensate for insulin insensitivity in type 2 pre-diabetes ?
**produces more insulin** to counteract the resistance of the insulin sensitive organs
95
What is the pathophysiology of type 2 diabetes ?
- **genetic defects** causing minor insulin resistance **paired with a bad lifestyle**
- **leads to raised insulin resistance**
- pancreas **secretes more insulin** to counteract this, but this **cannot be maintained forever without intervention**
- leads to hyperglycaemia = diabetes
96
Which glucose transporter is involved in insulin-mediated glucose uptake ?
GLUT**4**
97
True or false, GLP1R agonists are used as a treatment for diabetes ?
true
