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4) Metabolic Endocrinology > 14) Pancreas, Gastrointestinal Hormones and Leptin > Flashcards

14) Pancreas, Gastrointestinal Hormones and Leptin Flashcards

1
Q

What is central to many metabolic pathways?

A

Glucose

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2
Q

Which tissues are dependent on glucose as an energy source?

A
  • Neurons

- RBCs

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3
Q

The brain uses 60% of _________ glucose in the post-absorptive stage.

A

hepatic

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4
Q

How does gluconeogenesis vary in a day?

A

High late at night or early in the day

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5
Q

How does glycogenolysis vary in a day?

A

Increase in glycogenolysis between meals to deliver glucose

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6
Q

Hormones that affect glucose levels are affected by what three factors?

A
  • Appetite
  • Cell metabolism
  • Physiology of the GI tract
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7
Q

What are the major hormones of glucose control?

A
  • Insulin

- Glucagon

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8
Q

What are other hormones involved in glucose control?

A
  • Epinephrine
  • Cortisol
  • Growth hormone
  • Thyroid hormone
  • Secretin
  • Cholecystokinin
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9
Q

Which hormones act to lower blood glucose?

A

Insulin is the ONLY hormone that lowers blood glucose

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10
Q

What allows for the regulation of enzymatic activity?

A

Phosphorylation and dephosphorylation, allowing for the switching between an active and inactive state

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11
Q

What enzymes catalyze phosphorylation and dephosphorylation?

A
  • Phosphorylation: phosphokinases

- Dephosphorylation: phosphatases

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12
Q

Which type of receptor do glucagon and epinephrine utilize?

A

GPCR

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13
Q

Which type of receptor does insulin utilize?

A

Receptor with intrinsic tyrosine kinase activity

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14
Q

How many peptide hormones regulate the gastrointestinal tract?

A
  • More than 20 active peptides

- Forms one of the largest endocrine organs in the body

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15
Q

Which areas of the gastrointestinal tract are hormonally regulated?

A
  • Stomach
  • Intestine
  • Pancreas
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16
Q

Which gastrointestinal tract hormones are contained within the central or peripheral nervous system?

A
  • Somatostatin
  • Gastrin
  • Cholecystokinin
  • Insulin
  • Calcitonin
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17
Q

What is the function of gastrointestinal tract hormones are contained within the central or peripheral nervous system?

A
  • The function is unknown
  • They are produced in the cell body of neurons
  • May modulate signal transmissions (used as neurotransmitters)
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18
Q

What did Minkowski discover?

A
  • Observed diabetes in dogs after a pancreactomy

- Discovery of the abnormalities of the islets of Langerhans

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19
Q

What did Banting and Best discover?

A

Isolated insulin and demonstrated that it lowers blood glucose

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20
Q

What did Sanger discover?

A

Determined the amino acid sequence of insulin

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21
Q

What was the first recombinant hormone that was commercially marketed? When? How?

A
  • Insulin
  • 1982
  • Genetic engineering
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22
Q

Which hormones were discovered after insulin was uncovered?

A
  • Glucagon
  • Somatostatin
  • Pancreatic peptide
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23
Q

How many islets of Langerhans are there? What is their total weight?

A
  • 1 million

- 1 to 2 grams

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24
Q

What are the two types of cells contained in the exocrine portion of the pancreas?

A
  • Acinar cells

- Duct cells

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25
Q

What are acinar cells of the pancreas responsible for?

A

Secretion of digestive enzymes (protease, amylase, lipase)

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26
Q

What are duct cells of the pancreas responsible for?

A

Secretion of sodium bicarbonate

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27
Q

Differentiate the exocrine and endocrine portions of the pancreas.

A
  • Exocrine: empties into the duodenum

- Endocrine: releases hormones into the bloodstream

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28
Q

What do alpha-cells of the islets of Langerhans secrete?

A

Glucagon

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29
Q

What do B-cells of the islets of Langerhans secrete?

A

Insulin

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30
Q

What do D-cells of the islets of Langerhans secrete?

A

Somatostatin

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31
Q

What do F-cells of the islets of Langerhans secrete?

A

Pancreatic polypeptide

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32
Q

Which hormones are also produced by cells of the gastrointestinal mucosa? (3)

A
  • Glucagon
  • Somatostatin
  • Pancreatic polypeptide
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33
Q

Is the exocrine or endocrine portion of the pancreas highly vascularized?

A

Endocrine portion (islets of Langerhans) is highly vascularized

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34
Q

How does blood flow through an islet of Langerhans?

A

1) Blood is supplied to B-cells to detect glucose levels

2) Travels to peripheral alpha and delta cells

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35
Q

What is the function of the particular flow of blood through the islets of Langerhans?

A

Allows for the reaction of insulin prior to glucagon or somatostatin release

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36
Q

How does glucagon affect insulin and somatostatin?

A
  • Stimulates insulin

- Stimulates somatostatin

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37
Q

How does insulin affect glucagon?

A

Inhibits glucagon

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38
Q

How does somatostatin affect insulin, glucagon, and pancreatic polypeptide?

A

Inhibits insulin, glucagon, and pancreatic polypeptide

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39
Q

How is glucagon produced?

A

Preproglucagon is processed to proglucagon and glucagon

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40
Q

How does the size of glucagon compare to insulin?

A

Glucagon is smaller than insulin

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41
Q

How does an increase in blood glucose affect alpha and beta cells of the pancreas? What are the subsequent effects?

A
  • Inhibits alpha cells (decreases glucagon)
  • Stimulates beta cells (increases insulin)
  • Decreases blood glucose to normal
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42
Q

Which nutrients increase the release of insulin from B-cells?

A
  • Glucose
  • Amino acids
  • Keto acids
  • Fatty acids
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43
Q

Which gastrointestinal hormones increase the release of insulin from B-cells?

A
  • Gastrin
  • CCK
  • Secretin
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44
Q

How does growth hormone affect the release of insulin?

A

Stimulates

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45
Q

How does adrenaline affect the release of insulin?

A

Inhibits

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46
Q

How does cortisol affect the release of insulin?

A

Inhibits

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47
Q

How does glucagon affect the release of insulin?

A

Stimulates through a paracrine signal

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48
Q

How does somatostatin affect the release of insulin?

A

Inhibits through a paracrine signal

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49
Q

How do B-adrenergic and cholinergic autonomic nerves affect the release of insulin from B-cells?

A

Stimulates

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50
Q

Which nutrients increase the release of glucagon from alpha-cells?

A
  • Hypoglycemia

- Amino acids

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51
Q

Which nutrient decreases the release of glucagon from alpha-cells?

A

Free fatty acids

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52
Q

Which gastrointestinal hormones increase the release of glucagon from alpha-cells?

A
  • Gastrin
  • CCK
  • Gastric inhibitory peptide
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53
Q

Which gastrointestinal hormone decreases the release of glucagon from alpha-cells?

A

Secretin

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54
Q

How does growth hormone affect the release of glucagon?

A

Stimulates

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55
Q

How does adrenaline affect the release of glucagon?

A

Stimulates

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56
Q

How does insulin affect the release of glucagon?

A

Inhibits through a paracrine signal

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57
Q

How does somatostatin affect the release of glucagon?

A

Inhibits through a paracrine signal

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58
Q

How do adrenergic and cholinergic autonomic nerves affect the release of glucagon from alpha-cells?

A

Stimulates

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59
Q

Does environment, stress and starvation increase the release of insulin or glucagon?

A

Glucagon

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60
Q

What is the longest nerve in the human body?

A

Vagus nerve

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61
Q

Is the vagus nerve a sensory or motor neuron?

A

The vagus nerve acts as a sensory and motor neuron

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62
Q

How is the vagus nerve related to the gastrointestinal system?

A

It is the main neuronal coordinator of appetite control, digestion and metabolism

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63
Q

How is the vagus nerve associated with insulin?

A

Stimulates the release of acetylcholine in the pancreas, which stimulates insulin release

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64
Q

How do parasympathetic and sympathetic stimulation affect the secretion of insulin?

A
  • Parasympathetic stimulation stimulates insulin secretion

- Sympathetic stimulation inhibits insulin secretion

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65
Q

Which glucose transporter is used to mediate the uptake of glucose into the B-cells of the pancreas?

A

GLUT2

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66
Q

What is the effect of the entry of glucose into the B-cells of the pancreas on the ATP to ADP ratio?

A

Aerobic glycolysis increases glycolysis, which increases the ATP to ADP ratio

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67
Q

What is the effect of the alteration of the ATP to ADP ratio in B-cells of the pancreas?

A

Inhibition of ATP-sensitive potassium channels, which reduces potassium efflux, causing membrane depolarization

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68
Q

What is the consequence of membrane depolarization following glucose entry into B-cells of the pancreas?

A
  • Opening of voltage-gated calcium channels

- Increased intracellular calcium triggers exocytosis of insulin-containing granules

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69
Q

What occurs following the exocytosis of insulin-containing granules?

A

Opening of calcium-activated potassium channels leads to the repolarization of the membrane

70
Q

What factors generated during glucose metabolism facilitate exocytosis and/or proinsulin synthesis?

A

Metabolic coupling factors

71
Q

What are examples of metabolic coupling factors?

A
  • Plasma free-fatty acids

- Succinate

72
Q

How does GLP-1 potentiate the amplification pathway and exocytosis of insulin?

A

Binds to GLP-1 receptors and triggers cAMP production

73
Q

Which hormones are responsible for the hormonal regulation of the fasting state?

A
  • Glucagon
  • Adrenaline
  • Glucocorticoids
74
Q

What is serum glucose in the fasting state?

A

3 to 5 mM

75
Q

How does serum glucose vary after a meal? At what concentration does glycosuria occur?

A
  • 7 mM

- 10 mM (glycosuria)

76
Q

What are the anabolic effects of insulin?

A
  • Synthesis of protein, lipids and glycogen

- Inhibition of their degradation (usage of glucose)

77
Q

What are the three target tissues of insulin?

A

Liver, muscle, adipose tissue

78
Q

Glucagon increases many catabolic processes, particularly in the ________.

A

liver

79
Q

Why is the release of glucose from the liver tightly regulated between meals or at fast?

A

Because most tissues rely predominantly on glucose as an energy source

80
Q

How do free fatty acids vary in a glucose tolerance test?

A
  • Insulin increases, which stimulates lipogenesis

- Free fatty acids decrease

81
Q

How does growth hormone vary in a glucose tolerance test?

A

Glucose increases, which suppresses growth hormone

82
Q

How does glucagon vary in a glucose tolerance test?

A
  • Initially increases due to neural anticipatory stimulation

- Subsequently decreases with insulin suppression

83
Q

How does growth hormone affect glucose uptake and lipolysis?

A
  • Reduces glucose uptake

- Increases lipolysis

84
Q

How does glucose metabolism vary in a sleep-deprived and fully rested brain?

A

Greater glucose metabolism in a fully rested brain

85
Q

Where are GLUT2 receptors expressed?

A
  • B-cells of the pancreas
  • Liver
  • Small intestine
  • Kidney
86
Q

Where are GLUT3 receptors expressed?

A
  • Skeletal and cardiac muscle

- Adipose tissue

87
Q

Which GLUT receptor is insulin-stimulated?

A

GLUT4

88
Q

Where are GLUT4 receptors expressed?

A
  • Skeletal and cardiac muscle

- Adipose tissue

89
Q

How does insulin promote glucose uptake in muscle and adipose tissue?

A

By increasing GLUT4 transporters on the cell surface

90
Q

How does insulin promote glucose uptake in the liver?

A
  • Stimulating glucokinase
  • Promoting phosphorylation of glucose to form glucose-6-phosphate
  • Maintenance of the concentration gradient
91
Q

Which glucose transporter is present in the liver?

A

GLUT2

92
Q

What are the two pathways that are activated by the binding of insulin to its cognate receptor?

A
  • MAPK

- PI3K

93
Q

Which receptors may insulin cross-react with?

A

IGF-I

94
Q

Which receptors may IGF-I and IGF-II bind to?

A
  • Insulin
  • IGF-I
  • IGF-II
95
Q

GLUT_ is the insulin-responsive glucose transporter.

A

4

96
Q

The activation of ____ by insulin speeds the translocation of the GLUT4-containing endosomes into the cell membrane.

A

PI3K

97
Q

How many membrane-spanning domains does GLUT4 possess?

A

12

98
Q

What are the two GPCR pathways utilized by glucagon?

A
  • Gq

- Gas

99
Q

What are the two pathways that are affected by the activation of Gas by glucagon? (2)

A
  • Increase in PKA (increase in gluconeogenesis)

- Increase in phosphorylase kinase (increase in glycogenolysis)

100
Q

What pathway is affected by the activation of Gq by glucagon?

A
  • Increase in calcium

- Decrease in glycolysis and glycogenesis

101
Q

How does insulin affect fat stores?

A

Increase in triacylglycerol synthesis

102
Q

How does glucagon affect fat stores?

A

Increase in fatty acid mobilization

103
Q

(Glycogen synthase a/glycogen phosphorylase a) is favored in an insulin-dominant pathway.

A

Glycogen synthase a

104
Q

(Glycogen synthase a/glycogen phosphorylase a) is favored in an glucagon-dominant pathway.

A

Glycogen phosphorylase a

105
Q

Is glycogen synthase a or b phosphorylated? Which one is active? What is its function?

A
  • Glycogen synthase b is phosphorylated
  • Glycogen synthase a is active
  • Glycogen synthesis is favoured with glycogen synthase a
106
Q

Is glycogen phosphorylase a or b phosphorylated? Which one is active? What is its function?

A
  • Glycogen phosphorylase a is phosphorylated
  • Glycogen phosphorylase a is active
  • Glycogen breakdown is favoured with glycogen phosphorylase a
107
Q

Does insulin activate glycogen phosphorylase or glycogen synthase? Which one?

A

Glycogen synthase a

108
Q

Does glucagon activate glycogen phosphorylase or synthase? Which one?

A

Glycogen phosphorylase a

109
Q

Which enzyme catalyzes the conversion of glycogen synthase b to glycogen synthase a?

A

Phosphoprotein phosphatase

110
Q

Which enzyme catalyzes the conversion of glycogen phosphorylase a to glycogen phosphorylase b?

A

Phosphorylase a phosphatase

111
Q

Which enzyme catalyzes the conversion of glycogen synthase a to glycogen synthase b?

A

Protein kinase

112
Q

Which enzyme catalyzes the conversion of glycogen phosphorylase b to glycogen phosphorylase a?

A

Phosphorylase b kinase

113
Q

What are the effects of glucagon on islet cells of the pancreas?

A

Stimulates insulin secretion

114
Q

What are the effects of glucagon on the liver?

A
  • Stimulates glycogenolysis, gluconeogenesis, fatty acid oxidation and ketogenesis
  • Inhibits glycogen synthesis and fatty acid synthesis
115
Q

What are the effects of GLP-1 on islet cells of the pancreas in terms of insulin, somatostatin and glucagon?

A
  • Increases insulin secretion
  • Increases somatostatin secretion
  • Inhibits glucagon secretion
116
Q

How does GLP-1 affect B-cell mass?

A
  • Increases B-cell mass

- By inhibiting B-cell death and inducing B-cell proliferation

117
Q

How does GLP-1 affect the stomach?

A
  • Inhibits gastric acid secretion

- Inhibits gastric emptying

118
Q

How does GLP-1 affect appetite?

A

Inhibits appetite

119
Q

How does GLP-2 affect the intestine?

A
  • Stimulates mucosal growth and nutrient absorption

- Inhibits motility

120
Q

How does insulin affect plasma potassium?

A
  • Increases potassium intake into cell

- Plasma potassium decreases (hypokalemia)

121
Q

Glucose and insulin relieve (hypokalemia/hyperkalemia), and is effective to treat renal failure.

A

hyperkalemia

122
Q

How does insulin affect calcium flux?

A

Increase of calcium into the mitochondria

123
Q

How does an increase in calcium flux into the mitochondria increase fatty acid synthesis, ketone-body formation and entry into the TCA cycle?

A
  • May activate pyruvate dehydrogenase

- Increase the conversion of pyruvate to acetyl-CoA

124
Q

What is the pathology of T1DM?

A

Viral or autoimmune B-cell destruction

125
Q

What are different types of pathologies that may lead to T2DM? Give an example for each.

A
  • Pre-receptor resistance (e.g. antibodies against insulin)
  • Receptor resistance (e.g. decrease in insulin receptor number)
  • Post-receptor resistance (e.g. underexpression of B-cell glucose transporters)
126
Q

What is insulinoma?

A
  • Excess insulin secretion from B-cell pancreatic tumour

- Severe hypoglycemia

127
Q

What is the difference between slow- and fast-acting insulin?

A
  • Slow (long half-life)

- Fast (short half-life)

128
Q

How may insulin be administered?

A
  • Needles
  • Pens
  • Pumps
129
Q

What condition predisposes individuals to T2DM?

A

Obesity

130
Q

What factors may influence the incidence of T2DM?

A
  • Genetic vulnerability
  • Behavioural and lifestyle factors
  • Psychological factors
  • Demographic characteristics
131
Q

How does an increased quantity of fatty acids in the blood due to an increase in visceral adipose tissue affect T2DM?

A
  • Liver releases increased glucose and triacylglycerols, which leads to insulin resistance in peripheral tissues
  • Hyperglycemia leads to B-cell damage, which decreases production of insulin
132
Q

Why has there an increase in gastric bypass surgery in recent years?

A
  • Because the prevalence of obesity has increased

- Bariatric surgery allows for a significant decrease in weight

133
Q

What is the wait time for gastric surgery in Canada if an individual’s BMI is over 40?

A
  • 5 years in Canada

- 5 to 15 years in Quebec

134
Q

What are benefits of weight loss surgery? How does it affect diabetes specifically?

A

Resolves a number of issues related to metabolic syndrome, including T2DM

135
Q

How does somatostatin affect the pituitary?

A

Negative regulator of GH release

136
Q

How does somatostatin affect the pancreas? How does it act?

A
  • Inhibitor of insulin and glucagon secretion

- Acts in a paracrine fashion

137
Q

How does somatostatin affect the GI tract?

A
  • Inhibitor of the release of many GI hormones

- Additional direct inhibitory effects of GI functions

138
Q

How many amino acids are contained in somatostatin? How many different types of receptors are there? How many types of isoforms?

A
  • 14 amino acids
  • 5 receptors
  • 2 isoforms
139
Q

What are the main sources of circulating somatostatin?

A
  • GI tract

- Pancreatic D cells

140
Q

What are the main sources of pancreatic polypeptide?

A
  • Pancreatic F cells

- Between acinar cells of the pancreas

141
Q

How does pancreatic polypeptide affect appetite?

A

Reduces appetite

142
Q

How does pancreatic polypeptide affect the secretion of digestive enzymes of the pancreas?

A

Powerful inhibitor

143
Q

How does pancreatic polypeptide affect the gallbladder?

A
  • Blocks contraction of the gallbladder

- Inhibitor of bile secretion

144
Q

How does a meal affect the secretion of pancreatic polypeptide?

A
  • Increases after a meal and remains high for several hours

- Conservation of digestive enzymes and bile

145
Q

How may the increase of pancreatic polypeptide be mediated?

A

Vagus nerve and cholecystokinin in response to a meal

146
Q

How does an oversecretion of pancreatic polypeptide due to a tumour affect metabolic disturbances?

A

They are not associated with metabolic disturbances

147
Q

What produces gastrointestinal hormones in response to food intake?

A

Cells interspersed in the GI tract

148
Q

What is the action of gastrointestinal hormones on the central nervous system?

A
  • Appetite control

- GI motility

149
Q

What is the action of gastrointestinal hormones on the pancreas?

A

Stimulation of insulin and/or glucagon secretion

150
Q

What are incretins?

A

Group of metabolic hormones that stimulate a decrease in blood glucose levels

151
Q

Which gastrointestinal hormone was the latest to be discovered?

A

Ghrelin (2000)

152
Q

What are the functions of cholecystokinin?

A
  • Gallbladder contraction
  • Gastrointestinal motility
  • Pancreatic exocrine secretion
153
Q

What is the function of secretin?

A

Pancreatic exocrine secretion

154
Q

What is the major function of GIP?

A

Incretin activity

155
Q

How does ghrelin affect growth hormone release?

A

Increases growth hormone release

156
Q

Ghrelin is isolated from the ______, and consists of __-amino acids.

A

stomach

28

157
Q

What increases ghrelin secretion?

A

Fasting

158
Q

What decreases ghrelin secretion? (3)

A
  • Glucose
  • Growth hormone
  • Obesity
159
Q

How does ghrelin release vary in a day?

A
  • Increase with every meal

- Increase in the middle of the night

160
Q

How does dose-dependent ghrelin affect food intake in rodents?

A

Greater ghrelin results in a greater food intake

161
Q

How do ghrelin antagonists affect food intake in rodents?

A

Reduce food intake and body weight

162
Q

What is Prader-Willi syndrome? What are characteristic symptoms?

A
  • Excessive ghrelin secretion

- Individual is constantly hungry, which leads to obesity and T2DM

163
Q

What does proteolytic processing of proglucagon form in pancreatic alpha cells?

A

Glucagon

164
Q

What does proteolytic processing of proglucagon form in intestinal L cells?

A

GLP-1 and GLP-2

165
Q

Where is GLP-1 synthesized?

A

L-cells in the ileum and colon

166
Q

What is the half-life of GLP-1?

A

90 seconds

167
Q

How does GLP-1 affect the brain and nervous system in terms of appetite?

A
  • Decrease appetite

- Increase satiety

168
Q

How does GLP-1 affect glucose uptake and glycogen synthesis/breakdown?

A
  • Increase glucose uptake

- Increase glycogen synthesis

169
Q

How does GLP-1 affect the stomach?

A
  • Gastric emptying is decelerated

- Decrease acid secretion

170
Q

How does GLP-1 affect the secretions of the pancreas?

A
  • Increase insulin
  • Decrease glucagon
  • Increase somatostatin
171
Q

GLP-1 is an ______ since it enhances glucose-dependent insulin secretion.

A

incretin

172
Q

What mechanisms allow GLP-1 to amplify the release of insulin from stored granules?

A
  • cAMP
  • Ca2+
  • MAPK
  • PI3K

4) Metabolic Endocrinology (15 decks)

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