endocrine Pancreas Flashcards
1
Q
Outline the importance of maintaining plasma glucose levels
A
- Loss of insulin secretion or action will lead to diabetes
- Diabetes is high glucose concentration in the blood (hyperglycemia)
- High blood glucose=high salivary glucose leading to a greater risk of oral infections
- Normally blood glucose levels are around 4.5-5.5mmoles/l and is mainly sourced from the diet or gluconeogenesis (make new glucose which occurs in the liver and kidneys)
- Brain runs only on glucose therefor is highly susceptible to damage caused by hypoglycemia
○ Brain cannot use fatty acids for energy - If you are in a state of fasting/ starvation glycogen will be broken down in the liver into glucose
- Insulin can cause glucose to be stored in the muscle or fat for use or storage
*
2
Q
Describe the main features of the absorptive and post-absorptive states
A
- Absorbative=feeding
○ 5% Stored as glycogen (glycogenesis - liver and muscles)
○ 30-40% Converted to fat (adipose tissue and liver)
○ 50% Metabolized (Energy)- Post-absorptive=fasting
○ Breaking stuff down to maintain glucose level in the blood
○ Glycogen broken down (Glycogenolysis)
○ Glucose produced from amino acids and glycerol (Gluconeogenesis)
○ Glucose spared by fat breakdown and fatty acid release and energy source in non-neural tissues - Glucose can be taken up using liver into the skeletal muscle - glucose can be converted into glycogen for storage or be used immediately to create ATP
- Insulin is staffed or used int the liver
- Glucose is stored in the fat
- Most of your energy is used or stored in skeletal muscle, the other energy is stored or used in the liver and any remainder goes into the fat
- By product of fatty acid breakdown for energy is ketones, ketones will increase the acidity of the blood
○ Ketone E.g. acetone. Acetone smelling breath so diagnose type 1 diabetes
- Post-absorptive=fasting
3
Q
Name the hormones of the endocrine pancreas involved in regulating these states, describe their roles and the control of their release
A
- Glucagon
○ Released from the alpha cells
○ Used to increace the blood glucose levels
○ Used when the blood glucose concentration is too low (hypoglycemic)
○ Single polypeptide – 29 amino acids
○ release stimulated by:
▪ Low plasma glucose levels (starvation)
▪ Sympathetic activity (adrenaline)
○ release inhibited by:
▪ High plasma glucose
▪ Fatty acids
○ Action of glucagon on the liver
▪ Increases glycogenolysis
▪ Decreases glycogenesis
▪ Increases gluconeogenesis
▪ Increases fat breakdown
○ Action of glucagon on the adipose tissue
* increases fat breakdown
* Increases fatty acid release- Insulin
○ Released from the beta cells
○ Used to decrease the blood glucose levels
○ Used when the blood glucose concentration is too high (hyperglycemic)
○ Water soluble so can be carried in plasma with no need for transport proteins
○ Binds to receptors on the cell surface membrane
○ Has basal secretion + short pulses (constant small secretion and increased when eating)
○ Size of the plus/how much insulin is released is proportional to the rate of rise in plasma glucose (how much glucose has been eaten and how quickly it is being absorbed)
○ Stimulated by vagal stimulation and inhibited by sympathetic stimulation
○ To keep the blood glucose in a narrow range throughout the day, there is a low steady secretion of insulin overnight, fasting and between meals with spikes of insulin at mealtimes
○ Insulin acts on muscles, adipose tissue and liver and stimulates them to take up more glucose and subsequent use. It also increace glycogenesis in the liver and the muscles and increases fat synthesis in the liver and the fat. Insulin increases the amino acid transport into cells and protein synthesis- Glucose enters the pancreatic beta cells through the GLUT2 transporter
- Inside the beta cell glucose is converted into glucose-6-phosphate and used to produce ATP
- ATP causes ATP sensitive K+ channels to close causing depolarization that causes Ca2+ channels to open
- Increased cellular Ca2+ activates calcium-calmodulin dependent kinase stimulating exocytosis of insulin-containing granules
- Insulin is released into the blood
- Inulin also causes inulin mediated uptake of glucose
○ Causes vesicles containing GLUT4 to fuse with the plasma membrane and increace the number of GLUT4 carriers in the plasma membrane. This means that more glucose will be absorbed thought he GLUT4 transport proteins
○
- Insulin
4
Q
Describe the consequences of hyperglycemia with reference to diabetes mellitus
A
- Type 1 diabetes
○ Can be caused by: pancreatic beta islet cell destruction leading to absolute
insulin deficiency, autoimmune (most common), idiopathic (rare)….
○ Type 1 autoimmune distinction of beta cells in the pancreas
○ Usually occurs in children about 10-12 years old
○ Glucose stays in the blood as insulin is not released.
○ Body doesn’t know not to produce glucose so more glycogen and fat is broken down is broken down into glucose so glucose level increases
○ Fatty actin breakdown causes ketosis which lower blood PH
○- Type 2 diabetes
○ Has varying degrees of insulin resistance and insulin deficiency
○ Type 2 constantly eating food so body cells become resistant to insulin. Insulin is released but cells are resistant.
○ Little bit of insulin effect so usually don’t see ketosis
○ Difficult for patients to reverse only a few can do it
○ Other specific types:
▪ Maturity onset diabetes of the young (MODY)
▪ Genetic defects in insulin action
▪ Diseases of the exocrine pancreas (extensive disease, trauma, carcinoma, infection…)
▪ Endocrinopathies - includes acromegaly, Cushing’s syndrome glucagonoma and pheochromocytoma
* Caused by excess secretion of hormones which antagonize insulin including growth hormone, cortisol, glucagon and epinephrine
▪ Drug/chemical induced diabetes (e.g GCs, cyclosporin A)
▪ Infections (Congenital rubella, Coxsackie virus B etc) Classification of Diabetes - Consequence if diabetes
○ Muscle:
▪ Decrease uptake of glucose.
▪ Decrease glycogenesis.
▪ Decrease uptake of amino acids & protein synthesis (increace proteolysis)
○ Adipose tissue:
* Decrease uptake of glucose.
* Decrease lipogenesis and esterification.
* increace esterification (increace lipolysis).
○ Liver:
▪ Decrease glycogenesis & glycolysis.
▪ increace gluconeogenesis.
▪ increace gluconeogenesis from muscle amino acids.
▪ increace ketogenesis from adipose tissue fatty acids
○ Consequences:
▪ muscle wasting & weight loss.
▪ hyperglycaemia
▪ ketosis.
○○ - Acute symptoms
○ the Classic Symptoms – acute metabolic
▪ Polyphagia (frequently hungry)
▪ Polyuria (frequently urinating)
▪ Polydipsia (frequently thirsty)
○ Other symptoms might Include:
▪ Blurred vision
▪ Fatigue
▪ Weight loss
▪ Poor wound healing (cuts, scrapes, etc.)
▪ Dry mouth
▪ Dry or itchy skin
▪ Impotence (male)
▪ Recurrent infections such as vaginal yeast
▪ infections, groin rash, or external ear infections
▪ (swimmers ear)
▪ Acute Symptoms of Diabetes - Long Term Diabetic Complications
○ Chronic – microvascular disease:
▪ Diabetic retinopathy
▪ Diabetic nephropathy
▪ Diabetic neuropathy (peripheral nervous system)
□ Ulceration, gangrene - amputation
○ Chronic – macrovascular disease:
▪ coronary heart disease - major cause of death in diabetes
▪ peripheral vascular disease
▪ cerebrovascular disease
▪ Higher risk of bacterial infections
▪ Severe periodontal disease
▪ Dry mouth
▪ Slow healing after treatment
▪ Oral fungal infections§
- Diagnose
○ Oral glucose tolerance test (GTT)
§ Fasting levels 3.5-5.5mmol
§ Oral dose 75g Glucose
§ Post dose 7-9mmol
§ Returns to fasting level by 2 hours
○ HbA1c level
§ Indicates long-term
§ diabetes control.
§ Target <48 mmol/mol (<6.5%)
○
Describe the consequences of hypoglycemia - Hypoglycaemia - Blood glucose < 3.0mM
- Nervous system is rapidly affected
- Results in confusion, weakness, dizziness, and convulsions
- Hypoglycaemia triggers sympathetic activity
- Sympathetic signs lost in autonomic neuropathy
○ NO WARNING - Finally COMA AND DEATH
*
- Type 2 diabetes
