01 Thera VI DM Intro Gong Flashcards
What is the general definition of Type 1 Diabetes?
Pancreas makes too little or no insulin
What is the general definition of Type 2 Diabetes?
Cells do not use insulin well (insulin resistance). Ability for pancreas to make insulin decreases over time
What is the normal Islet function for glucose regulation when there is an increase in blood glucose?
Increase in insulin secretion (B-cell). Decrease in Glucagon secretion (a-cell)
What is the normal Islet function for glucose regulation when there is a decrease in blood glucose?
Decrease in Insulin secretion (B-cell). Increase in Glucagon secretion (a-cell)
What are the four main organs affecting plasma glucose insulin response?
Intestine (glucose absorption, cause Incretin release). Pancreas (insulin and glucagon secretion. Liver (glucose production and insulin action). Adipose tissue and muscle (glucose uptake insulin action)
What can C-peptide tell you about a patient?
C-peptide is the result from a cleavage creating insulin. If C-peptide is excessively high its an indication that your body is making too much insulin (usually a sign of type 2 DM (insulin resistance)). When C-peptide is too low it’s usually a sign that your body isn’t making enough insulin (type I DM)
What are the core defects resulting in Hyperglycemia?
Liver with increased Hepatic Glucose Production (HGP). Muscle cells with decreased glucose uptake. Pancreas with impaired insulin secretion and excess glucagon secretion
Besides the core contributors, what other organs can contribute to hyperglycemia?
GI tract with decreased Incretin effect. Increased lipolysis. Kidney with increased glucose reabsorption. Brain with neurotransmitter dysfunction. Islet a-cell with increased glucagon secretion
What are Incretins?
A hormone originating in the GI tract and released during nutrient absorption (food in stomach/intestines). Incretins augment insulin secretion at physiologic concentrations. The insulinotropic effects of Incretins are glucose dependent (do not cause hypoglycemia on their own). Some Incretins also decrease glucagon secretion from the a-cells
What is the general definition of GLP-1 and GIP?
Major Incretins in humans are Glucagon-Like Peptide (GLP-1) and Glucose-Dependent Insulinotropic Peptide (GIP)
What does GLP-1 do?
Increase insulin secretion and suppresses glucagon secretion. Regulates rate of gastric emptying. Affects CNS, resulting in increased satiety (sensation of fullness) and reduction of food intake
What does GIP do?
Increase insulin secretion
What are GLP-1 and GIP inactivated by?
Dipepidyl Peptidase 4 (DPP-4)
GLP-1 actions may extend beyond the pancreas. What other organs are affected?
Can increase cardio-protection and CO. Increases neuroprotection. Can actually increase B-cell proliferation and decrease B-cell apoptosis
Why is there a higher insulin response after PO glucose vs. IV glucose?
Glucose taken PO activate the Incretin Effect (Type 2 DM effect)
How does GLP-1 modulate insulin secretion?
GLP-1 potentiates glucose-dependent insulin secretion. GLP-1 enhances gene expression, synthesis, and release of insulin
How does GLP-1 also affect Insulin gene expression and B-cell function?
Upregulates insulin gene expression. Upregulates expression of genes essential for B-cell function. Promotes B-cell neogenesis and progenitor-cell differentiation (in animal models). Inhibits apoptosis (in animal models)
How does GLP-1 control glucagon secretion?
Suppresses glucagon release in glucose-dependent manner. Enhances glucagon release in response to hypoglycemia. Improves a-cell glucose sensing
What are the major Incretins?
GLP-1 and GIP
What is the major role of Glucagon?
Released from a-cells and have a positive effect on the liver, causing an increase in Hepatic Glucose Output (HGO). Ultimately increases glucose
What is the major role of Insulin?
Secreted by B-cells. Negatively acts on the liver, decreasing HCO. Acts positively on muscle cells/liver/fat cells to promote glucose uptake