Insulin and Diabetes Part 2

Mind Map by , created over 6 years ago

Endocrinology Mind Map on Insulin and Diabetes Part 2, created by maisie_oj on 04/21/2013.

Created by maisie_oj over 6 years ago
Pituitary Gland
Thomas Welford
The thyroid
Diabetes Mellitus
Geography Quiz - Tectonics
OP doplnovaci otazky II.
Helen Phamova
Nuclear receptors
Alix Stonehouse
ENDOCRINOLOGY (hypothalamus)
Alix Stonehouse
ENDOCRINOLOGY (growth hormone)
Alix Stonehouse
ENDOCRINOLOGY (thyroid gland)
Alix Stonehouse
Insulin and Diabetes Part 2
1 Symptoms of no/low insulin
1.1 Decreased anabolism
1.1.1 Hyperglycaemia Fatigue Glucosuria Osmotic diuresis Polydipsis (thirst) Water and salt depletion untreated
1.2 Increased catabolism
1.2.1 Increased glycogenolysis, gluconeogenesis an lipolysis Wasting/weight loss Hyperketonaemia and acidosis Vasodilation Hypotension and hypothermia Diabetic ketoacidosis Fatal if
2 Definition
2.1 Chronic
2.2 Elevated plasma glucose levels
2.3 Due to defects in insulin secretion and/or insulin action
3 Complications
3.1 Short-term
3.1.1 Hypoglycaemia
3.1.2 Diabetic ketoacidosis
3.1.3 Lactic acidosis
3.1.4 Diabetic coma
3.2 Long-term
3.2.1 Retinopathy Aneurysms and haemorrhages in retina
3.2.2 Nephropathy Nodular scarring (sclerosis) Blood vessels are compressed/distorted
3.2.3 Neuropathy Blood vessels around nerves become diseased and retract Nerves shrivel
3.2.4 Cardiovascular disease - atherosclerosis Increased fatty acids, triglycerides, VLDL, remnant particles and oxidised LDL particles (also small, dense LDL) Decreased HDL Postprandial (post-meal) hyperlipidemia
3.2.5 (Increased risk for pancreatic cancer?)
3.2.6 Ulceration
3.2.7 Dermatopathy
4 Type 1 Diabetes
4.1 Insulin dependent diabetes mellitus (IDDM)
4.2 Can occur in adulthood but usually presents earlier
4.3 Incidence - 1:250 people
4.3.1 3% increase in incidence each year
4.4 Due to autoimmune destruction of beta cells
4.5 Genetic and environmental causes
4.6 Evidence for autoimmune disease
4.6.1 T-lymphocyte infiltration of islet (insulitis)
4.6.2 Islet cell antibodies (ICAs) Insulin Glutamic acid decarboxylase (GAD)
4.6.3 Strong genetic association with HLA loci on MHC Class II
4.6.4 Associated with other autoimmune diseases (e.g. Hashimoto's thyroiditis)
4.6.5 Possible triggers for autoimmune disease Beta cell apoptosis Triggered by environmental factor (e.g. virus) Molecular mimicry Immune response to antigen with beta cell structural similarity Bystander activation Islet inflammation (due to viral infection) Stimulates beta cell specific T cells
4.7 Prevention and Therapy
4.7.1 Prevention with immunosuppression Anti-CD3 antibodies
4.7.2 Treatment Insulin Islet transplantation
5 Type 2 Diabetes
5.1 Occurs in adults <45 years
5.1.1 1 in 20 people
5.2 Accounts for 90-95% of diabetes
5.3 Defects in both secretion activation and secretion
5.4 Genetic component
5.4.1 100% concordance in monozygotic twins
5.4.2 Frequent in particular ethnic groups
5.5 Environmental component
5.5.1 Associated with sedentary lifestyle and high fat diet
5.6 Non-insulin dependent diabetes mellitus (NIDDM)
5.7 Impaired glucose tolerance
6 Hyperglycaemia and the Polyol Pathway
6.1 Reactive oxygen species form toxic aldehydes
6.1.1 Converted into inactive alcohols via aldose reductase AND NADPH to NADP+
6.2 Increased glucose converted into sorbitol
6.2.1 Becomes fructose via SDH and NAD+ to NADH
6.2.2 Via NADPH to NADP+ Converts oxidised GSSG to reduced GSH via glutathione reductase
6.3 Decreased NAD+ and increased sorbitol
6.3.1 Sorbitol causes osmotic stress
7 Hyperglycaemia and AGE Precursors


  • Really good paper alert!! F. Giacco and M. Brownlee, Oxidative Stress and Diabetic Complications, 2010
7.1 Increased glucose
7.1.1 Increased AGE precursors Intracellular protein glycation Abnormal interaction with matrix proteins and integrins (matrix receptors) Signal for intracellular transducers Altered gene expression
7.2 Production of modified AGE plasma proteins
7.2.1 Bind to RAGE (AGE receptors) Increased production of ROS NF-kappaB activation Changes to gene expression Altered function of AGE plasma proteins changes signal for intracellular transducers Altered gene expression
8 Hyperglycaemia and PKC
8.1 Increased glucose causes increased DAG and increased PKC (beta and delta isoforms)
8.1.1 Blood flow-abnormalities Decreased eNOS Increased ET-1
8.1.2 Vascular permeability and angiogenesis Increased VEGF
8.1.3 Capillary occlusion Increased TGF-beta causing increased collagen and fibronectin
8.1.4 Pro-inflammatory gene expression Increased NF-kappaB
8.1.5 Vascular occlusion Increased PAI-1 causing decreased fibrinolysis
8.1.6 Multiple other effects Increased NAD(P)H oxidases causing increased ROS
9 Hyperglycaemia and the Hexosamine Pathway
9.1 Increased glucose - becomes glucose-6-phosphate and then fructose-6-phosphate
9.1.1 Converted to glucoseamine-6-phosphate (instead of following glycolytic pathway) Converted into UDPGIcNAc (UDP-N-acetylglucoseamine) Addition of O-GlcNAc and (PO4)2- to serine and threonine residues at transcription factor sites (e.g. Sp1) Increased production of TGF-beta1 and PAI-1 (plasminogen activator inhibitor-1) Via GFAT (Glutamine:Fructose-6-phosphate aminotransferase) - inhibited by azaserine/AS-GFAT (antisense)

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