Diabetes Flashcards
What are the pancreatic endocrine glandular tissue and the cells they contain?
• Endocrine glandular tissue: pancreatic islets/ islets of Langerhans produce hormones
○ Alpha cells (α) produce glucagon = increase BGLs
○ Beta cells (β) produce insulin and amylin: insulin decreases BGLs & Amylin delays gastric emptying and suppresses glucagon post-meal
○ Delta cells (δ) produce somatostatin
Gastrin pancreatic polypeptide cells produce pancreatic polypeptides = stimulates gastric secretion
What are the pancreatic exocrine tissue and their function?
• Exocrine glandular tissue: produces digestive enzymes
○ ‘grape-like cells’ = effect alkaline fluids and digestive enzymes
○ Secretions are highly alkaline pancreatic juice, drained via the pancreatic duct, and neutralises the acidic chyme entering the duodenum from the stomach. These enzymes are secreted in their ‘inactive form’ of proteases (e.g. trypsinogen)
- Glycogenolysis:
- Gluconeogenesis:
- Glycogenesis:
- Lipogenesis:
- Lipolysis:
- Glycogenolysis: Glycogen → Glucose
- Gluconeogenesis: non-CHO → Glucose
- Glycogenesis: Glucose → Glycogen
- Lipogenesis: Glucose → Triglycerides
- Lipolysis: Fatty acids → Ketones
Human Endogenous Insulin:
Circulatory half-life of – - – minutes and ~–% is removed in a single pass through the liver. Basal insulin secretion (fasting state), maintains fasting plasma glucose levels between (4.4-5.6 mmol/L; normal <6.1 mmol/L). Stimulated insulin secretion during meals is increased due to levels of glucose, amino acids, — and PSNS (—-) stimulation. Inhibition of insulin secretion may occur due to hypoglycaemia, —- activation and —-
Human Endogenous Insulin:
Circulatory half-life of 3-6 minutes and ~50% is removed in a single pass through the liver. Basal insulin secretion (fasting state), maintains fasting plasma glucose levels between (4.4-5.6 mmol/L; normal <6.1 mmol/L). Stimulated insulin secretion during meals is increased due to levels of glucose, amino acids, FFA and PSNS (vagal) stimulation. Inhibition of insulin secretion may occur due to hypoglycaemia, SNS activation and PGE2
Metabolic Effects of Insulin:
Insulin is an —– hormone which:
• Stimulates ——- in skeletal muscle and liver (favours CHO storage)
• Inhibits ——– = decreases glucose output
• Inhibits ——— = conversion of non-CHO to glucose in the liver
• Promotes —– synthesis
• Inhibits degradation
* Insulin increases the transport of glucose into ----- tissue - precursor for the formation of ---- and ------ for triglyceride synthesis * Insulin promotes entry of ----- from the blood to ----- tissue cells and inhibits lipolysis = reduce release of FA from adipose tissue * Activation of -------- during digestion = decrease rate of meal being digested and absorbed. It can also restrain the movement of nutrients from the GIT into the blood = prolong gastric emptying time and decrease gastric acid and ------- production and reduces the contraction of the gallbladder
Metabolic Effects of Insulin:
Insulin is an anabolic hormone which:
• Stimulates glycogenesis in skeletal muscle and liver (favours CHO storage)
• Inhibits glycogenolysis = decreases glucose output
• Inhibits gluconeogenesis = conversion of non-CHO to glucose in the liver
• Promotes protein synthesis
• Inhibits degradation
* Insulin increases the transport of glucose into adipose tissue - precursor for the formation of FA and glycerol for triglyceride synthesis * Insulin promotes entry of FA from the blood to adipose tissue cells and inhibits lipolysis = reduce release of FA from adipose tissue * Activation of somatostatin during digestion = decrease rate of meal being digested and absorbed. It can also restrain the movement of nutrients from the GIT into the blood = prolong gastric emptying time and decrease gastric acid and gastrin production and reduces the contraction of the gallbladder
• β-cells are triggered by —- — —– = glucose taken up by the —-
• Glycolytic phosphorylation of glucose causes an —— in the ratio of ATP:ADP
*There is a difference GLUT in the pancreas vs skeletal muscle
• β-cells are triggered by rise in BGLs = glucose taken up by the glucose transporter 2 (GLUT2)
• Glycolytic phosphorylation of glucose causes an increase in the ratio of ATP:ADP
*There is a difference GLUT in the pancreas vs skeletal muscle
Insulin binds to the —- —- receptor on the —— of target cells (e.g. liver, skeletal muscle, fat) = induce signal transduction cascade = allows —– to transport glucose to the cell = glucose utilisation
Insulin binds to the kinase-linked receptor on the surface of target cells (e.g. liver, skeletal muscle, fat) = induce signal transduction cascade = allows GLUT4 to transport glucose to the cell = glucose utilisation
Metabolic Effects of Glucagon:
Acts on CHOs (2)
Acts on fats (3)
Acts on proteins (1)
Metabolic Effects of Glucagon:
• Acts on CHOs
○ Increase hepatic glucose production
○ Gluconeogenesis and glucose release = hyperglycaemic effects and promoting glycogenolysis
• Acts on fats:
○ Increase fat breakdown
○ Inhibits triglyceride synthesis
○ Increases ketogenesis (hepatic ketone production)
Acts on proteins = inhibits hepatic protein synthesis
What is Diabetes Mellitus?
- Dysfunction of the endocrine pancreas
- Disorder of CHO metabolism caused by a deficiency of insulin or resistance to the action of insulin
- Characterised by sustained/chronic hyperglycemia, polyuria, polydipsia, ketonuria and weight loss and other disturbances of CHO, fat and protein metabolism
- Estimated 1.2 million or 4.9% of Australians have DM
A diagnosis of DM is based on:
- Haemoglobin A1c (HbA1c) – glycosylated Hb ≥6.5%
- More than one fasting plasma glucose (FPG) level ≥7 mmol/L
- Plasma glucose in the 2-hour sample (2hPG) of the standard oral glucose tolerance test (OGTT) >11.1 mmol/L
- Random plasma glucose level ≥11.1 mmol/L
What is T1DM?
• Primary β-cell defect/ failure/ loss = absolute lack of insulin secretion = hyperglycaemia
- Result of a genetic-environmental interaction
What are the two distinct forms of T1DM?
• Immune (1A)
• Non-immune or idiopathic (1B)
*Sudden onset, between age 4-20 years, and a high incidence of complications requiring exogenous insulin administration. T1DM accounts for approximately 10% of all cases of DM
What is the pathophysiology of Immune T1DM?
Environmental or genetic factors result in cell-mediated destruction of pancreatic β-cells = markers of immune destruction (85-90% of individuals in fasting hyperglycemia) = auto-antibodies to islet cells (ICA) and/or insulin, glutamic acid decarboxylase (GAD) and protein kinase phosphatase
What is the pathophysiology of Non -Immune T1DM?
idiopathic; affects a small number of people (strongly inherited, no immune basis)
○ Unique natural history of genetic susceptibility/predisposition plus environment, immunologically-mediated destruction of β-cells and a long preclinical period
○ Exact nature of genetic susceptibility is poorly understood - strongest link to T1DM is the major histocompatibility complex (MHC) - glycoprotein molecules found on all cells except RBC. Alterations in MHC increases the risk of T1DM by 5-8 times
○ The environment, immunology and preclinical period usually occur as a result of exposure to viral infections (enterovirus), bovine serum albumin (a major constituent of cow’s milk) which leads to β-cell auto-antibodies, stress and puberty with a surge in growth hormone increases the risk of T1DM
○ Immunology and preclinical period: islet cell autoantibodies can be present for years before symptoms (long preclinical period rather than abrupt onset). Immune markers are found in 85-90% of cases of T1DM at clinical onset. Insulin auto-antibodies are also noted. Formation during islet cell and β-cell destruction. Before hyperglycaemia occurs, 80-90% of the function of these cells must be lost
What are the 3 poly’s of T1DM? What are the other clinical manifestations?
• Polyuria
• Polydipsia (thirst)
• Polyphagia (hunger)
Glucose accumulates in the blood and appears in the urine, causing polyuria and polydipsia. Protein and fat breakdown → polyphagia → weight loss
* Lethargy and fatigue * Poor use of food products * Sleep loss from nocturia * Skin infections (delayed wound healing) * Blurred vision * Ketoacidosis is also common
What are the diagnoses of T1DM and T2DM?
• Lab tests: measure BGL
T1DM - considered in 1st-degree relatives, obese individuals and >45 years
What is the treatment for T1DM?
successful management requires individual planning according to the type of disease, age and activity level. All T1DM individuals require a combination of:
• Insulin therapy
• Meal planning
• Exercise and self-monitoring of BGL
*Insulin types classified by length and peaking of action: rapid, short, intermediate, long-acting and premixed
What is T2DM?
Insulin resistance and/or inadequate insulin secretion/ deficiency = hyperglycaemia
