Session 10 ILO'S The endocrine pancreas and diabetes mellitus Flashcards
Describe how the ultrastructure of the β-cell relates to the synthesis and storage of insulin.
check discussion board, insulin synthesis slide of endocrine and pancreas and Glucose is the primary stimulator of insulin secretion slide
Beta cell has:
Many mitochondria - active proteins synthesis, storage and secretion all require energy
Extensive rough ER – active synthesis of protein for export
Extensive Golgi apparatus - active formation of hormone storage vesicles
Many storage vesicles - storage of large amounts of hormone ready for secretion
Many microtubules & microfilaments - active secretory tissue (exocytosis)
Describe the condition of Diabetes Mellitus / Define the condition Diabetes Mellitus
Diabetes is defined by an elevated blood glucose concentration (hyperglycaemia) which over time leads to damage of the small and large blood vessels causing premature death from cardiovascular diseases
- Occurs, due to insulin deficiency, insulin resistance, or both.
- Two main types (type 1 and type 2)
List the main differences between Type 1 and Type 2 Diabetes.
The 2 types are clearly distinguished by their epidemiology and probable causation, but not always so easily separated clinically
- T2 has a more gradual onset, whereas T1 is more sudden (type 1 due to autoimmune beta cell destruction)
- T2 is caused by insulin resistance and/or defective insulin secretory response whereas T1 is due to an absolute insulin deficiency /low or absent endogenous insulin
- T2 is normally adult onset (40 + usually), often obese individuals whereas T1 is more in early adulthood (less than 30, usually but not always young)
- T2 do not usually develop ketoacidosis, whereas T1 can develop ketoacidosis
- T2 is treated, at least initially with diet, drugs and exercise but T1 is treated with lifelong insulin
Describe and explain the typical pattern of presentation of Type 1 and Type 2 Diabetes.
T1: (7)
- Presents in early adulthood (but can be at any age)
- Thin or normal body habitus
- Sudden disease onset
- Low or absent endogenous insulin
- Presence of ketones
- Elevated plasma glucose
- Polyuria, polydipsia and weight loss
T2: (5)
- Presents later on in life (mostly adults)
- Generally obese
- Gradual disease onset
- Normal, decreased or increased insulin
- Can present with polyuria, polydipsia and weight loss but no urinary ketones (may be asymptomatic!)
Explain the sequence of events leading to ketoacidosis in the uncontrolled diabetic
Absence of insulin has a number of effects including:
- Increased rate of lipolysis in adipose tissue which releases large amounts of fatty acids, the substrate for ketone body formation
- Activation of the ketogenic enzymes in the liver
Both of which lead to increased ketone body production
Explain the causes and consequences of hypoglycaemia and hyperglycaemia
Causes of hypoglycaemia: (5)
- Taking too much insulin or diabetes medication
- Not eating enough.
- Postponing or skipping a meal or snack.
- Increasing exercise or physical activity without eating more or adjusting your medications.
- Drinking alcohol.
Causes of hyperglycaemia: (8)
- Not using enough insulin or oral diabetes medication
- Not injecting insulin properly or using expired insulin
- Not following your diabetes eating plan
- Being inactive
- Having an illness or infection
- Using certain medications, such as steroids
- Being injured or having surgery
- Experiencing emotional stress, such as family conflict or workplace challenges
Consequences of hypoglycaemia:
- Emergency as lack of glucose available to the vital organs (esp the brain, which needs glucose)
- Coma
- Activation sympathetic nervous system:
trembling, palpitations, sweating, anxiety, hunger, nausea and tingling (7) - Decreased levels of glucose to the brain: difficulty concentrating, confusion, weakness, drowsiness, vision changes, difficulty speaking, headache, dizziness and tiredness (9)
Consequences of hyperglycaemia:
Acute consequences:
- Metabolic decompensation
- Diabetic ketoacidosis (type 1)
- Hyperosmolar non-ketotic syndrome (type 2)
Describe, in broad outline, the principles of management of diabetes
Type 1 management:
- Lifelong insulin injections to replace missing endogenous insulin
Type 2 management:
- Diet – reduce glucose intake, reduce lipid intake
- Exercise – increase
- Drugs – lower blood glucose, lower blood lipids, insulin injections
Discuss the aetiology of metabolic syndrome and its consequences for health
Metabolic syndrome is a cluster of the most dangerous risk factors for cardiovascular disease which include:
- Diabetes (raised plasma glucose)
- Abdominal obesity
- High cholesterol
- High BP
= together, these factors increase the likelihood of cardiovascular disease
Generally, metabolic syndrome is caused by:
- Insulin resistance
- Central obesity
- Genetics
- Physical inactivity
- Aging
• For a person to have the metabolic syndrome:
• Waist measurement > 94cm for men and > 80 cm for women
• Plus any 2 of the following:
• Raised triglyceride > 1.7mmol/l or treatment
• Reduced HDL cholesterol <1.0 for men and 1.2mmol/l for
women
• Raised blood glucose > 135/85 or treatment
• Or raised fasting blood glucose > 5.6mmol/l or treated diabetes
List the common long term side effects of diabetes
Chronic consequences of diabetes:
- If prolonged diabetes can have microvascular and macrovascular complications
Microvascular complications
• Diabetic Retinopathy
• Diabetic Nephropathy
• Diabetic Neuropathy
• loss of sensation, erectile dysfunction, blindness, eye diseases, glaucoma, cataracts, foot ulceration/diabetic foot, painful peripheral neuropathy, constipation, diahhorea (10)
Macrovascular complications
• Cerebrovascular
• Cardiovascular
• Peripheral vascular disease
• stroke, heart attack, intermittent claudication, gangrene (4)
Describe the endocrine function of the pancreas.
• The pancreas secretes hormones to control the amount of sugar in your blood stream
• Two of the main pancreatic hormones are insulin, which acts to lower blood sugar, and glucagon, which acts to raise blood sugar.
• Endocrine function of pancreas occurs in islets of langerhans
• Cells of the islets of langerhans and what they secrete:
• Beta (β) cells - Insulin
• Alpha (α) cells - Glucagon
• Delta (δ) cells - Somatostatin
INSERT HISTOLOGY OF THIS from lecture 10.1
Explain the roles of insulin and glucagon in the control of metabolism.
Glucagon: (9)
- Dominates in fasted state and aims to raise plasma glucose
- Catabolic effects on the liver and adipose tissue
- Increase gluconeogenesis
- Increase glycogenolysis
- Increase ketogenesis
- The receptor for glucagon is GPCR
- Does not act on skeletal muscle - as it lacks glucagon receptors
- Water soluble (peptide hormones)
- Short half life of approx 5 mins (4-6)
Insulin: (10)
- Dominates in FED state and acts to lower plasma glucose (hormone of plenty)
- Anabolic effects in the liver, adipose tissue and skeletal muscle
- Increase glucose oxidation
- Increase glycogen synthesis
- Increase fat synthesis
- Increase protein synthesis
- The receptor for insulin is Tyrosine Kinase
- Glucagon Promotes translocation of GLUT4 to membrane in adipose and skeletal muscle, which promotes glucose uptake
- Water soluble (peptide hormone)
- Short half life of approx 5 mins (4-6)
Explain the principle and practice of measuring glycation of haemoglobin (amount of glucose in your blood) as an index of blood glucose control in the diabetic
Glucose reacts with the terminal valine of haemoglobin and forms glycated haemoglobin (HbA1c - just haemoglobin with glucose attached).
Extent of glycation depends on blood glucose concentration and half- life of haemoglobin (~60days)
High blood glucose = high HbA1c
Normal blood glucose = normal HbA1c (~5%)
Can be used to monitor an individual’s glucose control over the past 3 months
Describe what causes blood glucose to rise
•Inability to produce insulin due to beta cell failure and / or •Insulin production adequate but insulin resistance prevents
insulin working effectively and invariably linked to obesity
Describe what causes type 1 diabetes
- Autoimmune beta cell destruction
- Beta ells secrete insulin, so autoantibodies made are directed against the beta cells and insulin producing cells destroyed
Partly genetic predisposition: alleles of HLA-
DQB1, a MHC-II
We don’t quite understand what the trigger is
Describe the symptoms of diabetes/how it presents
Typical symptoms of hyperglycaemia:
• Polyuria, polydipsia, blurring of vision, urogenital infections - thrush
Symptoms of inadequate energy utilisation:
• Tiredness, weakness, lethargy, weight loss
The severity of these symptoms will depend upon the rate of rise of blood glucose as well as the absolute levels of glucose achieved
