Insulin Counter-Regulatory Hormones Flashcards by Costanza Coronelli

Low Glucose levels

No glucose transport
Glycogen + triglycerides not synthesised
Processes releasing glucose/FAs not inhibited

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Glucagon

Main hormone controlling blood glucose levels during fasting

Exact opposite to insulin

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Glucagon make up

29 amino acid peptide

Release from alpha cells of islets of Langerhans when glucose levels low

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Glucagon synthesis

Synthesised as large molecule= preproglucagon
Preproglucagon –> cleaved into many diff hormones depending on which cell it’s in
Cleaved into proglucagon
In pancreatic alpha cells, proglucagon –> glucagon

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Glucagon secretion

Increase in intracellular Ca2+

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Glucagon secretion stimulated by

Low blood glucose conc
Increased blood aa’s - especially arginine + alanine
Exercise –> in exhaustive exercise, glucagon conc increases 4-5x

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Glucagon secretion inhibition

Insulin

Somatostatin - released by delta cells in pancreas

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Glucagon receptor

G-protein coupled receptor

Contains 7 transmembrane domains coupled to trimeric G proteins

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Glucagon receptor activation

Glucagon binds
G proteins dissociate
Subunits trigger release of cAMP
–> increases Gluconeogenesis and Glycogenolysis
–> decreases Glycolysis and Glycogenesis

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Insulin + effect on Glucagon-depending signalling

Breaks down cAMP, which activates glucagon signalling cascade
Activates phosphodiesterase –> breaks down cAMP into AMP –> unable to activate signalling cascade

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Fasting

No insulin secretion
Liver releases glucose into bloodstream
Triglyceride stores deplete
B-Oxidation

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Fasting - no insulin secretion

cAMP downstream activates glycogenolysis

Break down of glycogen –> glucose

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Liver + glucose release

Glucagon increases gluconeogenesis
Glucagon inhibits Phosphofructokinase-1 and Pyruvate kinase
–> because of this, glycolysis stopped
–> gluconeogenesis ALLOWED
–> carbon based molecules converted into glucose in liver

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Triglyceride stores in fasting

Glucagon activates hormone sensitive lipase
Activates lipolysis
–> TGC –> glycerol + FAs

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Beta Oxidation

Lack of Malonyl-CoA (comes from glycolysis- inhibits FFA transport into mitochondria by inhibiting CPT-1)
FFAs can be shuttled in
Glucagon stimulates CPT1
–> activates Beta Oxidation

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Acetyl-CoA accumulation that can’t enter TCA

Converted into ketone bodies via Ketogenesis

Liver uses ketones to feed gluconeogenesis –> glucose for brain

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Adrenocortical hormones short term

Released from adrenal medulla
Released in response to stress + hypoglycaemia
Act V quickly
Main job is to increase glucose in blood to make sure can react to stressful situation

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Monoamines of adrenocortical hormone synthesis

Synthesised from phenylalanine and tyrosine

Epinephrine

Inhibits insulin secretion
Stimulates glycogenolysis in liver + muscle
Stimulates glucagon secretion
Increases lipolysis in adipose tissue
-->INCREASES BLOOD GLUCOSE + FA LEVELS

Adrenocortical hormones long term

Convert proteins + fats into glucose

Increase glucose conc in blood

Cortisol produced

Produced in adrenal cortex
–> Zona Fasciculatae
Derived from cholesterol

Adrenal cortex cells

Have many LDL receptors, enabling cholesterol uptake for steroid hormone synthesis
Secrete glucocorticoids + other steroids

Cortisol secretion

In response to adrenocorticotrophic hormone (ACTH) from pituitary, with a negative feedback loop
V strictly regulated
Stops its own release

Cortisol metabolic action long term

Enhances gluconeogenesis
Activates transcription of new genes for protein synthesis
Inhibits glucose uptake + utilisation
Stimulates muscle proteolysis
Stimulates adipose tissue lipolysis
–> rapid mobilisation of AA’s and FAs from cellular stores

Cortisol in resisting stress + inflammation

Helps maintain BP + Suppresses inflammation

Elevated cortisol levels for prolonged time

Can induce proteolysis + muscle wasting

Growth hormones

Can stimulate liver to produce insulin-like growth factor Act at level of: --> liver- gluconeogenesis --> adipose - lipolysis

Thyroid hormone mechanism

Similar to cortisol --> long term response | Activate nuclear receptors + transcription of large number of genes

Thyroid hormone release

very strictly controlled

Iodinated thyronines

Tetraiodothyronine, thyroxine (T4) | Triiodothyronine (T3)

Thyroid hormone bioactivity

Regulated by controlling conversion of T4-->T3 into target tissues T3= 4x more potent than T4

T3 in blood

Present in much smaller quantities than T4 | Persists for much shorter time

Thyroid hormone Metabolic Actions

Increases no. + activity of mitochondria --> increases ATP synthesis rate Stimulation of carbohydrate metabolism --> rapid glucose uptake, enhances glycolysis + gluconeogenesis, increased insulin secretion Stimulation of fat metabolism --> lipid mobilised rapidly from fat tissue, increased FA concentration in plasms Increased basal metabolic rate

Incretins

Group of gastrointestinal hormones GLP-1 Gastric inhibitory peptide Come from preproglucagon as well

GLP-1 Function

Inhibit glucagon secretion + hepatic glucose production Augments glucose-induced insulin secretion Increases insulin biosynthesis Slows gastric emptying Promotes satiety

Hypoglycaemia

Any abnormality low plasma glucose concentration that exposes the subject to potential harm Proposed Threshold plasma glucose value <70mg/dL

Hypoglycaemia reasons

Stimulation of glucose utilisation | Inhibition of glucose release

Hypoglycaemia causes

``` High insulin doses Alcohol excess (inhibition gluconeogenesis) Insulinoma Excessive exercise Reactive hypoglycaemia ```

Mild hypoglycaemia symptoms

``` <70mg/dL causes autonomic symptoms Trembling Palpitations Sweating Anxiety Hunger Tingling ```

Moderate hypoglycaemia symptoms

``` <55mg/dL cause autonomic symptoms + neuroglycopaenic symptoms Difficulty concentrating Confusion Weakness Drowsiness Vision changes ```

Severe hypoglycaemia symptoms

``` <40mg/dL is MEDICAL EMERGENCY Confusion Disorientation Convulsion Fitting Seizures loss of consciousness coma ```

Prolonged hypoglycaemia

Growth hormone + cortisol secreted - -> decrease rate of glucose utilisation by most cells - -> Convert to fat utilisation

Prolonged hypoglycaemia consequences

Serious consequences related to neuroglycopenia (shortage of glucose for brain) Permanent brain damage Loss of cognitive function, seizures + coma

Severe Hypoglycaemia

``` Diabetic emergency Can occur in patients using blood glucose lowering medication or prandial glucose regulators Missed or delayed meal Overdose on medication Exercise without medication adjustment Alcohol consumption ```