Insulinoma Case Flashcards
Fasting blood glucose levels
normal fasting [glucose]: 70-100 mg/dL
hypoglycemia: < 54 mg/dL
hyperglycemia (e.g. diabetes mellitus, metabolic syndrome): > 110 mg/dL
Insulin
Insulin: UPregulates anabolism.
stimulates cells to take up glucose from the blood; reduces blood glucose concentration
increases glycogen synthesis
increases protein synthesis
increases glycolysis and fatty acid synthesis
blocks glucagon release
Glucagon
Glucagon upregulates catabolism.
When “hungry”. . .
Glucagon: blocks glucose uptake
increases glycogenolysis and lipolysis
increases gluconeogenesis
Insulin and glucagon half-lifes in blood stream
Very short - 5 minutes
How do insulin and glucagon time curves compare to glucose?
Insulin nearly mirrors glucose. Glucagon is inversely related.
Why did the paramedics ask the patient if anyone in the house had diabetes medications around?
To learn if of the possibility of intentional or unitentional consumption of medications that might lead to the patients high levels of insulin/low glucose levels
What’s the significance of the elevated C-peptides in the patients blood?
As proinsulin becomes insulin, C-peptides detach and are released in the blood. Because this patient’s C-peptides are up, we can safely determine that her elevated insulin levels are not from medication, which would not include C-peptides.
Where is insulin produced?
Islets of langerhans; region of pancreas containing endocrine cells, specifically beta cells
How does the pancreas release insulin?
Glucose enters pancreatic beta cells via GLUT2. Glycolysis –>TCA–>EC–>ATP. ATP blocks K+ pump stopping charge gradient the K+ pump usually creates by pumping K+ out of cells. The disruption in voltage signals Ca++ gate to let Ca++ in. Ca++ inside beta cells activate release of insulin by storage vesicles into bs
Through a long series of reactions, insulin triggers cells to take up glucose. In general how?
Insulin activates phosphatases which, through a long series of reactions, cause conformational changes leading to recruitment of GLUT4 to take up glucose into cell.
Describe the process of insulin maturation
INSULIN IS A PROTEIN. Preproinsulin (104AAs) Proinsulin 3* strux, (84AAs) Insulin (51AAs). Normally, C peptide is cut out b/w proinsulin and insulin. Insulin heaxamer forms with Zn2+.
We sent our patient home with a continuous glucose monitoring system. Why didn’t blood-glucose levels rise after lunch and dinner, and only minimally after breakfast?
The patient’s insulinoma turned led to a chronic release of insulin into the blood. Hence the high C-peptide levels.
Blood glucose levels never really had a chance to catch up.
Normally, how is blood glucose concentration maintained after dietary carbohydrates are exhausted?
Normally the liver maintains glucose concentrations in the blood through. . .
glycogenolysis
gluconeogenesis
Both processes are activated by glucagon.
Only hepatocytes express glucose 6-phosphatase; this allows them to export glucose.
Why else was glucose chronically low?
Insulin and glucose are inhibitors of glucagon release. Because the patients insulin was overproduced, glucagon was not being released to turn on glucogenolyis and glyconeogenesis
The “hungry hormone”
Glucagon release into circulation from pancreatic alpha cells is stimulated by low glucose concentration, low levels of insulin. Release is also stimulated by cortisol, epinephrine, and norepinephrine.
Glucagon signals through a heterotrimeric G protein coupled receptor which results in mobilization of cAMP.
