ENDO V Flashcards
A cells/α cells -
Glucagon
B cells/β cells -
Insulin
D cells/δ cells -
Somatostatin
F Cells –
Pancreatic Polypeptide
The pancreas
contains ~–
million islets of
Langerhans.
1-2
α cells and β
constitute about
–% of the cells in
the islets.
85
he majority of the
pancreas is composed of
Acinar Cells produce
Digestive Enzymes
Exocrine Portion
Insulin secretion is associated
with
energy abundance.
Insulin is composed of
two amino acid
chains, connected by disulfide
linkages.
When A & B chains are —,
functional activity of insulin
molecule is lost
split
The proinsulin and C peptide
have virtually
no insulin activity
Insulin circulates entirely in
unbound form. T1/2 =
6min
Formation of Insulin occurs in –
cells. It is first made as proinsulin.
β
In the Golgi, proinsulin is
cleaved to form
C
peptide and insulin
Incretins are
hormones produced by the digestive system that work to
stimulate insulin secretion BEFORE plasma glucose is elevated.
incretins include (2)
Glucagon-like Peptide-1 (GLP-1)
Glucose-dependent Insulinotropic Polypeptide (GIP).
The sulfonylurea receptor (SUR) receptor (KATP channel) is the binding site for some drugs that act as
insulin secretagogues (ex. Glimepiride/Amaryl) for treatment of type 2 Diabetes Mellitus.
Glucose is the key regulator of insulin secretion; glucose levels >-- mmol/L (70 mg/dL) stimulate insulin synthesis.
3.9
(5) also
influence insulin secretion.
Amino acids, ketones, various nutrients, gastrointestinal peptides, and neurotransmitters
Tyrosine Kinase-linked receptor
• Target cells responses: (3)
1. Fast (seconds): Increased glucose uptake, especially by muscle cells and adipocytes due to translocation of vesicles containing GLUT-4 to the membrane. The membrane also becomes more permeable to many amino acids along with potassium and phosphate ions.
- Slower (10-15 minutes): Change
in enzyme activity leading to
changes in metabolism. - Slowest (hours-days): Changes
in gene expression and growth.
Insulin promotes muscle glucose — and metabolism-
anabolic effect
uptake
– Resting muscle
membrane only
slightly
permeable to glucose
– Insulin stimulation
increases
glucose
transport
Effects of Insulin on Muscle
increase (2)
– Increases glycogen storage in skeletal muscle – Increases protein synthesis and inhibits protein degradation
Effect of Insulin on Protein Metabolism & Growth
Promotes — — and
Storage Inhibits — —
Protein Synthesis
Protein Degradation
Lack of insulin
causes protein
depletion &
increased
plasma amino
acids.
Insulin promotes the uptake and storage of
glucose (as
glycogen) by the liver
nsulin promotes the uptake and storage of glucose (as
glycogen) by the liver
Mechanisms: (3)
• increases glucose uptake (glucokinase)
• increase glycogen synthase lead to increased glycogen synthesis
• decrease breakdown of glycogen by inhibiting liver
phosphorylase
Insulin promotes conversion of excess glucose into
fatty
acids
insulin inhibits
gluconeogenesis
Insulin Promotes Fat (2)
Synthesis and Storage
Insulin Promotes Fat Synthesis and Storage:
· increase glucose transport into liver
-TG+ lipoprotein released from liver
· activates lipoprotein lipase in the capillary walls of adipose tissue
- splitting triglycerides into fatty acids
- absorption into adipocytes
Essential effects of insulin for
fat storage in adipose tissue:
· Inhibits action of
· Enhances glucose transport into
hormone-sensitive lipase
adipocytes
- α glycerol phosphate
- glycerol+ fatty acids to TG
Lack of insulin causes (2) and
increases (2)
lipolysis and
release of FFA (Diabetic Ketoacidosis)
plasma cholesterol
and phospholipids conc.
increase Insulin Secretion (9)
Increased blood glucose
Increased blood free fatty acids
Increased blood amino acids
Gastrointestinal hormones (gastrin, cholecystokinin,
secretin, GIP, Glucagon-like peptide-GLP-1)
Glucagon, growth hormone, cortisol
Parasympathetic stimulation; acetylcholine
β-Adrenergic stimulation
Insulin resistance; obesity
Sulfonylurea drugs (glyburide, tolbutamide
Decrease Insulin Secretion (5)
Decreased blood glucose Fasting Somatostatin α-Adrenergic activity Leptin
Glucagon
• – amino acid peptide, secreted from
29
pancreatic alpha cells
Glucagon
hormone of
starvation
Glucagon
secretion controlled by
blood glucose levels (inverse relationship)
Glucagon
primary target tissue
liver
Glucagon targets liver to increase blood glucose by (3)
- Stimulating glycogenolysis & inhibiting
glycogen synthesis - Increasing gluconeogenesis
- Increases blood fatty acid & ketoacid
levels to provide more substrates for
gluconeogenesis
The liver functions like a
buffer for
blood glucose. Individuals with severe liver disease have difficulty maintaining a narrow plasma glucose range.
Glucagon secretion is stimulated by (3)
Hypoglycemia,
Epinephrine (β2), Vagus
Nerve
Diabetes Mellitus (DM) Definition
Metabolic disorder characterized by
hyperglycemia due to insufficient insulin or
cellular resistance to insulin (or both)
With DM, it takes longer to
reduce blood glucose levels
and glucose levels don’t
reach the
control level.
DM Major classifications (2)
- Type 1 Diabetes-10% of cases-hypoinsulinemia
2. Type 2 Diabetes-90% of cases-hyperinsulinemia
Symptoms of Diabetes Mellitus (8)
• Urinating often (Polyuria) • Feeling thirsty (Polydypsia) • Feeling hungry (Polyphagia) • Extreme fatigue • Blurry vision • Cuts/bruises that are slow to heal • Weight loss – even though you are eating more (type I DM) • Tingling, pain or numbness in the hands/feet (type 2)
These are the three
classic symptoms and
are called the 3 P’s.
- Urinating often (Polyuria)
- Feeling thirsty (Polydypsia)
- Feeling hungry (Polyphagia)
Approximately 25% of patients with type 1 diabetes mellitus
initially present in
diabetic ketoacidosis (hyperglycemia >250 mg/dl, ketosis and metabolic acidosis with anion gap).
Diagnosis of Diabetes Mellitus (2)
Casual plasma glucose ≥200 milligrams/dL (11.1 mmol/L) and
symptoms of hyperglycemia
Diabetes Mellitus Type I
Pathophysiology (3)
- Autoimmune destruction of pancreatic beta cells
- Accounts for 5-10% of diabetes cases
- Formerly called juvenile onset diabetes or insulin dependent diabetes (IDDM)
Diabetes Mellitus Type I Risk Factors (3)
. Genetic predisposition-increased susceptibility
- Environmental triggers stimulate autoimmune response
a. Viral infections (mumps, rubella)
b. Chemical toxins - Usually develops < age 40, non-obese younger patients
Manifestations of DM Type I (3)
- Beta cell destruction occurs slowly
- Hyperglycemia occurs when 80 – 90% of cells destroyed
- Often triggered by stressor (e.g. illness)
Hyperglycemia leads to: (7)
- Polyuria (hyperglycemia acts as osmotic diuretic)
- Polydipsia (thirst from dehydration from polyuria)
- Polyphagia (hunger and eats more since cell cannot utilize glucose)
- Glycosuria (renal threshold for glucose exceeded)
- Weight loss (body breaking down fat and protein to restore energy source
- Malaise and fatigue (due to muscle & electrolyte loss)
- Hyperkalemia-K+ (due to lack of insulin which normally activates the Na+/K+ pump)
Diabetic Ketoacidosis (DKA) • Due to i
ncreased lipolysis to fatty acids to produce ketoacids
DKA is a response to
cellular starvation brought on by relative insulin deficiency and counterregulatory or catabolic hormone excess (glucagon, catecholamines, cortisone and growth hormone).
DKA Pathophysiology (3)
- Osmotic diuresis & dehydration (hyperglycemia)
- Metabolic acidosis (accumulation of ketones)
- Fluid and electrolyte imbalances (from osmotic diuresis)
Signs and Symptoms of DKA (9)
– Fruity breath (due to acetone) – Nausea/ abdominal pain – Dehydration – Tachycardia – Lethargy – Coma – Polydipsia, Polyuria, Polyphagia – Kussmaul respirations (deep, labored breathing) • Blow off carbon dioxide to reverse acidosis
There are three categories of
the severity of DKA:
1. Mild (pH 7.25-7.3)- the individual is alert 2. Moderate (pH 7.0-7.25)- the individual will be drowsy 3. Severe (pH less than 7.0)- the individual will be in a stupor or coma.
Remember that acidosis
depresses neuronal function
since it blocks inward current of (2)
Na+ and Ca2+
Diabetes Mellitus (DM) Type II
Fasting hyperglycemia despite availability of insulin-Insulin
resistance
Diabetes Mellitus (DM) Type II was called
non-insulin dependent diabetes or adult onset
diabetes. Both misnomers, type II DM may require insulin
and occurs in children.
SKIPPED
Risk Factors for DM Type II
• History of diabetes in parents or siblings
• Obesity (especially of upper body)
• Physical inactivity
• Race/ethnicity: African American,
Hispanic, or American Indian origin
• Women: history of gestational diabetes,
polycystic ovarian syndrome, delivered
baby with birth weight > 9 pounds
• Patients with hypertension; HDL
cholesterol < 35 mg/dL, and/or triglyceride
level > 250 mg/dl.
Pathophysiology of T2DM
early
late
Hyperinsulinemia due to insulin resistance (early)
Beta cell dysfunction with impaired insulin secretion-
pancreatic exhaustion? (late)
Pathophysiology of T2DM Due to (2)
downregulation of insulin receptors in target
tissues & insulin resistance
Insulin resistance is part of a cascade of disorders
that are called METABOLIC SYNDROME. (5)
- Obesity, especially abdominal deposition
- Insulin resistance
- Fasting Hyperglycemia
- Lipid Abnormalities (High TG and Low HDL)
- Hypertension
ndividuals with metabolic
syndrome have increased risk
for
cardiovascular disease (CVD), particularly atherosclerosis and insulin resistance is a contributing factor for development of type 2 DM.
Pathophysiology of T2DM
similar chronic complications as
type 1
Retinopathy:
leading causes of blindness in the
United States
Nephropathy:
progressive renal dysfunction that
can lead to end-stage renal disease.
Neuropathy:
peripheral loss of sensation and
dysesthesias
Vascular disease:
accelerated atherosclerotic cerebrovascular and peripheral vascular diseases may occur due to abnormal lipid metabolism
Myopathies:
progressive weakness and
diminished exercise tolerance.
Oral Manifestations of DM (7)
- Periodontal Disease
- Salivary and taste dysfunction
- Oral bacterial and fungal infections (ex. candidiasis)
- Oral mucosa lesions (geographic tongue, lichen planus, etc.)
- Diminished salivary flow and burning mouth syndrome (with poor glycemic control)
- Delayed mucosal wound healing
- Xerostomia in patients on oral hypoglycemic agents
Diabetes mellitus: linked to — disease
periodontal
Periodontal disease exacerbates diabetic
complications (2)
– poor glycemic control
– cardiovascular complications (stroke,
ischemia, infarction)
Control of periodontal infection may
improve — control
glycemic
