DM Case Flashcards
Where is insulin produced in the cell?
The pancreas, specifically the β cells of the islets of Langerhans, is responsible for insulin synthesis and secretion
What is the primary physiologic stimulant of insulin?
Glucose
What is the function of GLUT2?
GLUT-2: facilitates glucose entry into the β cells, which creates an equilibrium between extracellular and intracellular glucose concentrations. This is a non-insulin dependent process.
What is the function of glucokinase?
Glucokinase: an enzyme within the mitochondria which controls the first step in glucose metabolism leading to the production of ATP
Glucokinase controls the first step of glucose metabolism by producing ATP. What does the ATP do?
ATP inhibits the K+ channel which prevent K+ from leaving the cell leading to cell membrane depolarization and Ca2+ influx
Briefly describe the structure of C peptide.
Proinsulin, consists of A and B chains joined by a 31-amino acid known as C peptide
C-peptide is cleaved to form insulin prior to release from β cells. A measure of the amount of C peptide is equivalent to the amount of insulin.
What is the consequence of membrane depolarization and Ca2+ influx into the cell?
Promotes passive release of insulin from the b cells.
Explain the mechanism of action of insulin.
Insulin receptor is composed to α and β subunits
Insulin binds to the α subunit, which activated tyrosine kinase of the β subunit
Receptor activation is the first critical step in a cascade of intracellular events that begins with phosphorylation of multiple docking proteins (IRSs)
Once activated, these multifunctional proteins initiate complex intracellular signaling pathways
Binding of IRS to phosphatidylinositol 3-kinase (PI-3K) initiates the major pathways including translocation of the glucose transporter (GLUT-4) to the cell surface and the inactivation of glycogen synthase kinase 3 (GSK3)
Binding of IRSs also activate the MAP kinase pathway and the mitogenic effects of insulin
What are the metabolic effects of insulin on the following tissues and organs?
o Adipose tissue decrease in glucose uptake increase in lipogenesis decrease in lipolysis o Muscular tissue increase in glucose uptake decrease in glycogen synthesis increase in protein synthesis o Liver decrease in gluconeogenesis decrease in glycogen synthesis increase in lipogenesis
Describe the function of GLUT-4 glucose transport protein.
Glucose transport in peripheral tissue requires normal insulin binding to its receptor and signaling of the GLUT-4 glucose transport protein which translocates glucose to the cell surface
What is the role of glucagon?
o Produced by the pancreatic α cells
o Insulin’s antagonist
o Simulates hepatic glucose production (gluconeogenesis)
What are incretins?
Gut-derived peptides, including glucagon-like peptides, that stimulate insulin secretion
Glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP) increase in response to a meal
Dipeptidyl peptidase-4 (DPP-IV) is responsible for the metabolism of GLP
How is glucose reabsorbed by the kidneys?
Normally filtered at the glomerulus and reabsorbed at the proximal tubule via the SGLT1 and SGLT2 transporter, so that none appears in the urine
Ninty percent of the filtered glucose is reabsorbed by the high capacity SGLT2 transporter in the convoluted proximal tubule
The remaining 10% of the filtered glucose is reabsorbed by the SGLT1 transporter in the descending proximal tubule.
Define DM
Diabetes mellitus refers to a group of metabolic disorders characterized by hyperglycemia
- Abnormal carbohydrate, fat and protein metabolism
- Leading cause of blindness and end-stage renal disease
- Increases risk of mortality
Type 1 diabetes: 11 times greater
Type 2 diabetes: 2-4 times greater
What is the criteria for classification and diagnosis of Hyperglycemia?
Table 1: Criteria for Classification/Diagnosis of Hyperglycemia
Fasting Plasma Glucose (FPG) or Impaired Fasting Glucose Test (IFG)
Normal < 100 mg/dL
Pre-diabetes 100-125 mg/dL
Diabetes > or equal to 126 mg/dL
2-hour plasma glucose (PG) during 75-g Oral Glucose Tolerance Test (OGTT) [mg/dL] or Impaired Glucose Tolerance test (IGT)
Normal < 140 mg/dL
Pre-diabetes 140-199 mg/dL
Diabetes > or equal to 199 mg/dL
A1c [%]
Normal < 5.6%
Pre-diabetes 5.7-6.4
Diabetes > or equal to 6.5%
Random PG [mg/dL] > 200 mg/dL+ classic symptoms
*In the absence of unequivocal symptoms of hyperglycemia, should be confirmed by repeat test on a different day; can “mix and match” lab tests for diagnosis
