Fuel Metabolism and Pancreatic Hormones

pancreas, insulin, glucagon, amylin, somatostatin

the ______ plays a vital role in the digestion, storage, and use of fuels; it is an endocrine gland which produces _______, _______, _______, and ________

endocrine

the ______ pancreas, an anatomically small portion of the pancreas (1-2% of total mass) produces hormones involved in regulating fuel storage and use

exocrine, exocrine

the pancreas also serves as an ______ gland, secreting pancreatic enzymes; cells of the _______ pancreas produce and secrete digestive enzymes and fluids into the upper part of the small intestine

islets of Langerhans

the endocrine pancreas consists of numerous clusters of cells, known as the _______ _____ _______

-amylin

-ghrelin

-glucagon

-insulin

-somatostatin

the islets of Langerhans contain specific types of cells responsible for the synthesis and secretion of the hormones:

Islets of Langerhans

the _____ _____ _____ are the functional units of the endocrine pancreas

β, α, δ, F, ε

the ____ cells secrete insulin and amylin; the ____ cells secrete glucagon; the _____ cells secrete somatostatin; _____ cells secrete pancreatic polypeptide (PP); the recently discovered mammalian ____ cells produce ghrelin

β

______ cells are the most numerous cell type of the islet, comprising 70-90% of the endocrine cells; they typically occupy the most central space of the islets and produce insulin, proinsulin, C-peptide, and amylin

amylin

______ is a newly described protein, also known as islet amyloid-associated peptide

insulin

______ orchestrates body fuel metabolism both during periods of fasting and during feeding

α, proglucagon

______ cells are generally located near the periphery, where they form a cortex of cells surrounding the more centrally located β cells; they express the ________ gene, processed to yield glucagon

L, glucagon-like peptide 1

proglucagon gene is also expressed in the intestinal ____ cells and processed to yield _____-_____ _____ ____ (GLP-1), GLP-2, and several spacer or intervening peptides in the gut

29, gluconeogenesis, glycogenolysis

pancreatic glucagon is a ____-amino acid peptide that regulates plasma glucose levels via effects on ________ and ________

δ

_______ produce somatostatin in the pancreas

hypothalamus, 14, 28, 28, 14

in both δ cells and the ______, somatostatin exists as _____-amino acid and _____-amino acid peptides; in δ cells, the ______-amino acid peptide predominates, and in the hypothalamus the _____-amino acid peptide form is predominant

C, insulin

the ___-terminal 14 amino acids deliver the biologic activity of somatostatin; as blood flows from the centrally located β cells to the peripherally residing α cells, the endocrine effect of somatostatin on ________ secretion is minimalized

F

_____ cells are the least abundant of the hormone-secreting cells of islets; the represent about 1% of the total cell population in the pancreas and produce PP

reduces, increases, inhibit

PP ______ gastric acid secretion and _______ intestinal transit times by reducing gastric emptying and upper intestinal motility; it appears to _______ the secretion of the exocrine pancreas

PP

transgenic mice that overexpress _____ exhibit reduced weight gain and decreased fat mass

glucose

_______ is the most important physiologic factor in the regulation and synthesis of insulin

glucose

insulin secretion and biosynthesis are stimulated when the islets are exposed to ________; the metabolism of glucose by the β cell triggers both of these events

5, 10, enhanced

studies document that within minutes after raising plasma glucose levels, the rate of proinsulin biosynthesis increases ____-fold to ____-fold; at the molecular level, an _______ efficiency of proinsulin translation in the β cells following glucose exposure

ribosomes, 110

insulin is first synthesized by ______ of the RER as a larger precursor peptide; this peptide is then converted to the mature hormone prior to secretion; the insulin gene product is a _____-amino acid peptide called preproinsulin

86

proinsulin consists of _____ amino acids

basic, C-peptide

in the process of converting proinsulin to insulin, two pairs of ______ amino acid residues are clipped out of the proinsulin molecule; that results in the formation of insulin and ____-______, which are secreted from the β cell in equimolar amounts

dose-related

glucose stimulated insulin secretion is ______-_____

oral, IV, oral

dose-dependent increases in insulin release have been observed after ______ and ______ glucose loads; the insulin secretory response is greater after _______

incretin effect, enhance

known as the _____ ______, this enhanced response to oral glucose is an indication that absorption of glucose by the GI tract stimulates the release of hormones and other mechanisms that ultimately ________ the sensitivity of the β cells to glucose

true

true or false: insulin secretion does not respond as a linear function of glucose concentration

IV, biphasic

when glucose is infused _____ at a constant rate, there is a ______ secretory response; that response consists of a rapid, early insulin peak followed by a second, more slowly rising peak

rapid, slow

glucose given intravenously promotes a ______ rise in plasma glucose concentration; in contrast, the oral glucose challenge induces a ______ rise in plasma glucose concentration

rapid, presynthesized, acute, chronic

sensing a _____ rise in plasma glucose concentration, the β cells first secrete their stores of _______ insulin; following this ______ phase, the cells begin to secrete newly synthesized insulin in the _______ phase, which lasts as long as the glucose challenge

GLUT2

the glucose transporter _______ mediates movement of glucose into the β cell

glucokinase

the first rate-limiting step in this process is the phosphorylation of glucose to glucose-6-phosphate by the enzyme _______

glycolysis, insulin, ATP

there is considerable evidence that glucokinase, by determining the rate of _______, functions as the glucose sensor of the β cell; this is the primary mechanism by which ________ secretion adapts to changes in blood glucose; ______ is synthesized during this process

Ca2+, exocytosis

that effect increases cytosolic ______, which is the main spark for the release of insulin into the circulation via _______

blood glucose

the primary regulator of glucagon secretion is _____ ______

somatostatin

_______ inhibits glucagon and insulin secretion

fed, deficit

while insulin is secreted in the ______ state, glucagon is secreted in response to an overall _______ in the nutrient supply

carbohydrate, fat

insulin is the primary regulator of ______ and _____ metabolism and controls the storage of these nutrients as well

amino acid, growth, apoptosis

besides metabolism of glucose and lipid, signaling by insulin affects other processes such as _______ _____ transport and metabolism, protein synthesis, cell ______, differentiation, and ________

liver, skeletal muscle, adipose

the three principal targets of insulin action are the ______, ______ ______, and _______ tissue

glycogen, triglycerides

glucose carbon is stored in the body in two primary forms: ________ and _________

glycogen

_______ is a short-term storage form that plays an important role in maintaining normal blood glucose levels; it is stored primarily in the liver and skeletal muscle

glycogen synthase

insulin activates ______ ______ by dephosphorylation, promoting glycogen synthesis and inhibiting its breakdown

enhances, hexokinase, pyruvate, pyruvate

insulin _______ glycolysis; it also activates the enzymes glucokinase (liver), _______ (muscle), phosphofructokinase, _______ kinase, and ________ dehydrogenase of the glycolytic pathway

-stimulates amino acid uptake

-increases activity of several factors involved in protein synthesis; also increases the amount of protein synthesis machinery in cells by promoting ribosome synthesis

-inhibits protein degradation by reducing lysosome activity and possibly other mechanisms as well

insulin promotes protein accumulation in its primary target tissues (liver, adipose tissue, muscle) in three specific ways:

liver

glucagon influences the metabolism of carbohydrates, lipids, and proteins primarily in the _______

glycogenolysis

glucagon produces a net effect of glycogen breakdown (________) by increasing intracellular cAMP levels and inactivating glycogen synthase

gluconeogenesis

glucagon stimulates hepatic _________ by increasing the enzyme phosphoenolpyruvate carboxykinase (PEPCK)

ureagenesis

glucagon stimulates _______, a process that assists in the disposal of ammonia by increasing the activity of the urea cycle of enzymes in liver cells

ketones, glucose

_______ are an important source of fuel for muscle cells and heart cells during times of starvation; during prolonged starvation, the brain adapts its metabolism to use ketones as a fuel source; that effect lessens the overall need for hepatic _______ production

insulin/glucagon

______/______ ratio determines metabolic status; in most instances, these hormones produce opposing effects; therefore, relative levels of both hormones in the blood plasma determine the net physiologic response

fed, fasting, 100

the I/G ratio is the highest in the _____ state and is the lowest during ________; it can vary by _____-fold or more because the plasma concentration of each hormone can vary considerably in different nutritional states

type 1 diabetes

a good example of the influence of the I/G ratio on metabolic status is in ______ ______ ______