SM_184b: Intermediary Metabolism Flashcards
Insulin is a ___ hormone with a short half life released from ___
Insulin is a peptide hormone with a short half life released from beta cells in the Islets of Langerhans
Insulin receptors are ____
Insulin receptors are tyrosine kinases
Describe process that occurs after insulin binds to insulin receptors
Process that occurs after insulin binds to insulin receptors
- Insulin binds to insulin receptors (RTKs)
- Glucose uptake in target tissues by transposition of membrane glucose transporter GLUT-4
- Stimulation of glycogen synthesis and inhibition of glycogenolysis in the liver
- Induction of genes regulating storage of energy carriers in the form of glycogen and triglyceride synthesis, mainly in muscle and liver
- Induction of genes responsible for increased protein synthesis (anabolic)
Insulin dependent tissues are ____, ____, and ____
Insulin dependent tissues are muscle, fat, and liver
Insulin is continually synthesized by ____
Insulin is continually synthesized by beta cells in the Islets of Langerhans
(secreted from beta cells)
____ is produced in equimolar concentration from insulin’s precursor proinsulin and released along with insulin
C-peptide is produced in equimolar concentration from insulin’s precursor proinsulin and released along with insulin
____ are a better marker for endogenous insulin production than insulin given the longer half life of c-peptide
Serum C-peptide levels are a better marker for endogenous insulin production than insulin given the longer half life of c-peptide
____ is the main regulator of the rate of insulin release from secretory vesicles
Plasma glucose level is the main regulator of the rate of insulin release from secretory vesicles
Describe the mechanism for regulation of insulin release via plasma glucose
Mechanism for regulation of insulin release via plasma glucose
- Plasma glucose is sensed by beta cells via free entry of glucose in beta cells (GLUT 2 transporter)
- Oxidative metabolism of glucose via glycolysis and entering the Krebs cycle (citric acid cycle) leading to production of ATP
- Resulting increase in ATP / ADP ratio is sensed by ATP sensitive potassium channels on the cell membrane of beta cells (KATP channels)
- KATP channels are inhibited and increase their rate of closure in response to a rising ATP / ADP ratio -> higher rate of depolarization
- Cell depolarization activates VG-gated Ca channels -> rise in cellular [Ca] via Ca entry into the cell membrane, augmented by Ca release from ER (triggered by the initial Ca influx)
- Rise in intracellular [Ca] triggers fusion of insulin and c-peptide containing vesicles with the cell membrane exocytosis of prestored insulin and c-peptide
- Additional factors facilitate or inhibit insulin release and production from beta cells
___ facilitates insulin release from beta cells
GLP-1 facilitates insulin release from beta cells
Glucagon is secreted by ____ in the ____
Glucagon is secreted by alpha cells in the Islets of Langerhans
Describe action of glucagon
Glucagon
- Counteracts insulin with respect to glucose uptake and metabolism
- Stimulates insulin secretion from beta cells -> prevents excessive hyperglycemia in response to glucagon
Ghrelin is released mainly by cells in the ____ and ____
Ghrelin is released mainly by cells in the stomach and intestinal wall
Ghrelin levels rise during ____, inducing ____ and promoting ____
Ghrelin levels rise during fasting, inducing hunger and promoting energy conservation
____ is secreted by adipose tissue proportional to its mass
Leptin is secreted by adipose tissue proportional to its mass
___ induces satiety
Leptin induces satiety
(sensitivity to leptin’s effect may be decreased in persons with chronic obesity)
Inactivating mutations in the genes encoding either ____ or the ____ lead to massive obesity
Inactivating mutations in the genes encoding either leptin or the leptin receptor lead to massive obesity
(currently being explored for treatment of obesity and / or diabetes)
_____ is secreted by cells in the intestine in response to food intake and facilitates insulin secretion from beta cells following oral intake
Glucagon like peptide 1 (GLP-1) is secreted by cells in the intestine in response to food intake and facilitates insulin secretion from beta cells following oral intake
GLP-1 agonists are used for the treatment of ____
GLP-1 agonists are used for the treatment of diabetes mellitus
Fed state involves higher ____ levels and lower ____ levels
Fed state involves higher insulin levels and lower glugoxe levels
In the ___ state, glucose uptake, protein, glycogen, and triglyceride synthesis is stimulated in insulin sensitive target tissue (liver, muscle, adipocytes)
In the fed state, glucose uptake, protein, glycogen, and triglyceride synthesis is stimulated in insulin sensitive target tissue (liver, muscle, adipocytes)
In the fed state, lower levels of orexigenic hormones such as ____ and higher levels of ____ promote satiety
In the fed state, lower levels of orexigenic hormones such as ghrelin and higher levels of leptin promote satiety
In the fasting state, ____ levels are maintained in the normal range by decreasing plasma insulin levels, while there are higher ___ levels
In the fasting state, glucose levels are maintained in the normal range by decreasing plasma insulin levels, while there are higher glucagon levels
In the fasting state, ___ is released from the liver
In the fasting state, glucose is released from the liver
(glycogenolysis, gluconeogenesis)
In the fasting state, ____ are mobilized from adipose tissue and either oxidized in peripheral tissue or converted to ketones in the liver
In the fasting state, liver are mobilized from adipose tissue and either oxidized in peripheral tissue or converted to ketones in the liver
In the fasting state, ____ are mobilized from body protein stores and serve as substrate for liver ____
In the fasting state, amino acids are mobilized from body protein stores and serve as substrate for liver gluconeogenesis
In the fasting state, higher levels of orexigenic hormones such as ____ and decreasing levels of ____ promote hunger
In the fasting state, higher levels of orexigenic hormones such as ghrelin and decreasing levels of leptin promote hunger
____ and ____ are increased in the fasting state
Glucagon and ghrelin are increased in the fasting state
____ and ____ are increased in the fed state
Insulin and leptin are increased in the fed state
Describe principle hormones of the Islets of Langerhans
Islets of Langerhans
- Glucagon: alpha cells
- Insulin: beta cells
- Somatostatin: d cells
- Pancreatic polypeptide: F cells
____, ____, and ____ stimulate glucose secretion while ____ and ____ inhibit insulin secretion
Glucose, GLP-1, and glucagon stimulate glucose secretion while inflammatory cytokines and norepinephrine inhibit insulin secretion
Describe the importants about insulin
Insulin
____ and ____ inhibit glucagon secretion
Glucose and insulin inhibit glucagon secretion
GLP-1 and GIP are ____, act through ____, and are degraded by ____
GLP-1 and GIP are peptide hormones secreted by the L-cells in the jejunum in response to feeding, act through GPCR, and are degraded by several peptidases including DPP-4
Describe effects of GLP-1 and GIP
GLP-1 and GIP
- Enhance glucose stimulated insulin secretion
- Inhibit glucagon secretion
- Delay gastric emptying
- Induce satiety
Leptin is a peptide hormone mainly secreted by ____ and acts through ____
Leptin is a peptide hormone mainly secreted by adipocytes and acts through cytokine activated cell membrane receptor class (JAK / STAT mediated)
Ghrelin is a peptide hormone secreted by ____ and ____
Ghrelin is a peptide hormone secreted by epsilon cells (Islets of Langerhans) and gastric cells
Ghrelin has effects of ____ and ____
Ghrelin has effects of inducing hunger and decreasing energy expenditure
___ has greatest energy density
Fat (9 kcal/g) has greatest energy density
Carbohydrates and proteins: 4 kcal/g
Insulin increases with ___
Insulin increases with meals
(returns to higher baseline level of insulin resistance)
