The key role of glucose, Metabolic syndrome and diabetes

Question 1

GLUCOSE

Brain consumes 80% ____. Blood cells and kidney
nearly 20%
Ingested and manufactured- gluconeogenesis
and ________. Blood levels controlled
by insulin

Answer 1

GLUCOSE

Brain consumes 80% NIMGU. Blood cells and kidney
nearly 20%
Ingested and manufactured- gluconeogenesis
and glycogenenolysis. Blood levels controlled
by insulin

Question 2

Islet on Langerhans cells

Answer 2

Delta cell: Somatostatin
B cell: Insulin
Alpha cell: Glucagon.
F cell: Pancreatic polypeptide

Question 3

GLUT 1 RBC BRAIN NIMGU
*GLUT 2 \_\_\_\_\_ and \_\_\_\_\_ (also NIMGU, glycolysis occurs)
GLUT3 NEURONS (PLACENTA)
*GLUT 4 \_\_\_\_\_ and \_\_\_\_\_ –insulin
mediated and present in vesicles (also
exercise induced)

Answer 3

GLUT 1 RBC BRAIN NIMGU
*GLUT 2 PANCREAS AND LIVER 
GLUT3 NEURONS (PLACENTA)
*GLUT 4 FAT AND MUSCLE –insulin
mediated and present in vesicles (also
exercise induced)

Question 4

Cellular insulin release of beta cells

drugs, sulphonyl urea, GLP1 enzyme breakdown inhibitors,

Answer 4

• Glucose enters- NIMGU and through GLUT2. Also GLP1
• Glucokinase phosphorylates and glyocolysis
• Closure of K+ channel
• Opening of Calcium channel
• Insulin release

Question 5

Insulin structure, clinical point

Answer 5

A and B chain.

C chain removed when proinsulin-insulin, can be measured when present with hypoglycaemia

Question 6

How does insulin signalling result in glucose uptake by muscle cells

Answer 6

Insulin binds, then post receptor activated. Phosphorylation cascade, causes translocation of GLUT4 to surface

Question 7

Insulin regulation

Answer 7

Rises: Increased glucose, glucagon, vagus nerve stim, release of GLP1

Decreases: Falling glucose, sympathetic nerve stimulation. somatostatin, adrenaline, GH, cortisol

Question 8

Insulin action

CARBS:
 1. \_\_\_- inhibits \_\_\_\_\_ and
\_\_\_\_\_\_
2. Muscle-increase \_\_\_\_ transport
and \_\_\_\_\_\_. Glycogen synthesis
3. Adipose tissue-same as \_\_\_\_\_

PROTEIN:
_____ by increasing transport of
AA into liver and muscle

FAT

• Increases triglyceride storage and inhibits _____ (↓hormone sensitive lipase)and ___ production
• Inhibits ____ production

Answer 8

CARBS:
 1. Liver- inhibits glyogenolysis and
gluconeogenesis
2. Muscle-increase glucose transport
and glycolysis. Glycogen synthesis
3. Adipose tissue-same as muscle

PROTEIN:
Anabolic by increasing transport of
AA into liver and muscle

FAT

• Increases triglyceride storage and inhibits lipolysis (↓hormone sensitive lipase)and FFA production
• Inhibits ketone production

Question 9

Energy storage

Answer 9

Fat, 80% of stored energy, not available straight away

Carbs make up 1-2 of stored energy but rapidly available

Question 10

How does muscle contribute to gluconeogenesis

Answer 10

Glyocogenolysis and lactate formed goes into the COri cycle, goes to the liver where it is converted to glucose

Question 11

krebs cyce

Answer 11

Glucose to pryuvate (Glycolysis) to acetyl CoA.
Acetly Coa goes into cycle to form 38 ATP.
Lactate and alanine from protein hydrolysis can enter the cycle.
From lipolysis, glycerol can enter but FFA can not. FFA’s oxidised to ketones.

Question 12

Ketones

___ oxidation
Fuel for ____ and muscle, not acutely by ____ and RBC’s
Insulin deficency = hormone sensitive ____ unlocked.
Uncontrolled _____ and protein hydrolysis
____ inactive.

Results in diabetic ketoacidosis (dehydrated, hypotensive)

Answer 12

FFA oxidation
Fuel for liver and muscle, not acutely by brain and RBC’s
Insulin deficency = hormone sensitive lipase unlocked.
Uncontrolled gluconeogenesis and protein hydrolysis
GLUT4 inactive.

Results in diabetic ketoacidosis (dehydrated, hypotensive)

Question 13

Hypoglycaemia signs

Answer 13

Autonomic activation Sweating, tremor

Cognitive dysfunction

Question 14

Hypoglycaemia causes

Answer 14

Insulin with diabetes patient (hypoglycaemic unawareness)
Sulphonylurea treatment
Insulinoma
Severe hormone deficiency (Addisons, cortisol deficiency)

Question 15

What describes insulin resistance, and what is it associated with.

Three things to look for

Answer 15

Given concentration of insulin, with a suboptimal response)
Associated with: Obesity, Type 2 diabetes, Endocrine disorders (Cushings, acromegaly), Metabolic syndrome

Metabolic cluster, PCOS, acanthosis nigricans

Question 16

What are the key components of the metabolic syndrome?

Answer 16

Central obesity, hypertension, abnormal glucose, high TG, low HDL

Question 17

What causes insulin resistance

Answer 17

Increased visceral fat, large adipocytes are resistant to insulins ability of suppressing lipolysis. Increases non esterified FA’s. These aggravate IR in muscle and liver

Also increased adipnectin ad resistin

Question 18

Insulin resistance consequences

Glucose: ____ glucose not suppressed, glucose uptake in muscle reduces. Only _____ to keep normal glucose. B cell toxicity.
Fat: Rise in ____ adipocytokines. B cell toxicity.

B cell starts to fail, poor ____ ____ insulin release
Alpha cell _____ and ______

Answer 18

Glucose: Hepatic glucose not suppressed, glucose uptake in muscle reduces. Only hyperinsulinaemia to keep normal glucose. B cell toxicity.
Fat: Rise in FFA, adipocytokines. B cell toxicity.

B cell starts to fail, poor first phase insulin release
Alpha cell dysregulation and hyperglucagonaemia

Question 19

Diabetes mellitus

fasting glucose mesure and HbA1c

Answer 19

Metabolic disorder characterised by presence of hyperglycaemia and defective insulin secretion, action or both

7mmol/L, HbA1c > 50

Question 20

Micro and macrovascular complications of diabetes

Answer 20

Macro: IHD, PVD, stroke
Micro: Retinopathy, perpheral neuropathy, nephropathy