Diabetes mellitus 1 (Block 5) Flashcards
Pancreas
Glandular organ in digestive and endocrine system of vertebrates
Pancreas - exocrine gland
Secretes enzymes that aid digestion and absorption of nutrients
Pancreas - endocrine gland
Synthesises important metabolic hormones, like insulin, glucagon, and somatostatin
What types of cells control exocrine secretions released into the pancreatic duct?
Ductal cells
Acinar cells
Ductal cells
Release bicarbonate
Acinar cells
Synthesis and release enzymes
Islets of Langherhans
Clusters of endocrine cells in the pancreas
Closely associated with local capillary network
Main role = regulating glucose metabolism & blood glucose concentration
Islets of Langerhans - cell types
Alpha cells - release glucagon
Beta cells - release insulin
Delta cells - release somatostatin
Gamma cells - release pancreatic polypeptide
Where does insulin act?
Liver
Muscle
Fat
Insulin
Peptide hormone
2 chains of amino acids linked by disulphide bridges
First protein ever to be sequenced
Diabetes mellitus
Excess blood glucose (hyperglycaemia) or an inability to control blood glucose levels
Acute clinical signs of diabetes
Glycosuria
Polyuria
Polydipsia
Type 1 diabetes
Chronic autoimmune disorder
Immune system attacks insulin-secreting beta cells in the pancreas -> insulin deficiency
Cause unknown
Insulin replacement therapy required
Acute consequences of T1 diabetes
Thirst, excessive urine production
Blurred vision
Weight loss
Fatigue
If untreated -> ketoacidosis, dehydration, coma, death
Chronic consequences of T1 diabetes
cardiovascular disease
Kidney disease
Eye problems
Peripheral neuropathy
Poor peripheral circulation leading to lower limb amputation
Treatment of T1D
Insulin replacement therapy
Difficult to mimic physiological insulin secretion
Cannot traditionally be given orally
Treatment of T1D - recombinant human insulin
Insulin gene inserted into E. coli
Large scale production of human insulin in vitro
Monitor serum glucose
Administer required amount of insulin by subcutaneous injection (i.m. or i.v. in emergency)
Units of insulin tailored to food intake
Physiological release of insulin
Continuous basal release accounts for ~50% of daily insulin release
Remaining ~50% is released in high-level bursts in response to food intake
Modern treatment of T1D attempts to mimic this pattern
Short-acting and immediate insulins
Regular insulin
Neutral protamine Hagedorn (NPH)
Regular insulin
Native human insulin protein in solution
Short-acting
NPH (Neutral Protamine Hagedorn)
First synthesised in 1936 using porcine insulin; now human
Suspension of crystalline zinc insulin combined with the positively charged polypeptide, protamine
Intermediate; onset 1-4hrs, peak 6-10hrs, duration 10-16hrs
Rapid-acting insulins
Created by minor modifications to amino acid sequence
Compared to regular insulin: higher peak insulin level, time to reach peak level reduced, duration of effect reduced
Long-acting insulins
Changes to amino acid sequence and/or addition of lipophilic side chains
Compared to regular insulin: lower peak insulin level (or no peak), time to reach peak level extended, duration of effect greatly enhanced
Mixed insulins
Variety of mixed insulin formulations have been developed
Improve adherence with treatment & reduce number of injections
Traditionally: regular and NPH insulins mixed immediately prior to injection
Later: rapid-acting formulations provided as a pre-mix with NPH
i.e. 30:70 aspart to NPH and 25:75 lispro to NPH
Recently: premix of 30:70 aspart to degludec has been licensed in EU
Do not allow adjustment of individual constituents
