endocrine-pancreas Flashcards
Glucose production primarily in the ____ (gluconeogenesis)
liver
CNS uses ____ of all blood glucose at rest, 25% of total
60%
Skeletal muscle uses glucose for rapid activity, ____ energy from fat at rest
85%
RBC require____.
glucose
Most tissues can use ____ and___.
glucose and fat
β cells secrete___.
insulin
α cells secrete ____.
glucagon
δ cells secrete _____(inhibits release of gastrin, CCK, secretin)
somatostatin
Balance between insulin and glucagon activity normally maintains blood glucose between____, whether in a fasting or postprandial (after eating) state
~60 and 140 mg/dL
Insulin is an ______, i.e., it promotes building new tissue and energy storage
anabolic hormone
what is insulin secreted by?
Secreted by pancreatic β-cells
Insulin release is stimulated by
Glucose (primary stimulus, amino acids to a lesser extent) Several hormones: Gastric inhibitory polypeptide (GIP) Glucagon-like peptide-1 (GLP-1) Growth hormone (pregnancy, puberty, adolescence) Estrogens (pregnancy, puberty) Melatonin Leptin
Practically speaking, insulin only affects glucose metabolism in what three tissues?
Liver
Adipose tissue
Muscle
Insulin Stimulatory Effects in liver
Protein, fatty acid and glycogen synthesis
Insulin Stimulatory Effects in adipose tissue
Glucose and fatty acid uptake
Triglyceride synthesis and storage
Insulin Stimulatory Effects in muscle
Glucose uptake
Protein and glycogen synthesis
Insulin Inhibitory Effects in liver
Ketogenesis and gluconeogenesis
Insulin Inhibitory Effects in adipose tissue
Lipolysis
Insulin Inhibitory Effects in muscle
Proteolysis
______ is a polypeptide secreted by α-cells of the pancreatic islets of Langerhans
Glucagon
Glucagon is a _____ hormone which increases blood glucose when glucose is not being absorbed
catabolic
glucagon secretion is Promoted by ______.
hypoglycemia and elevated blood amino acids, gastric inhibitory peptide (GIP)
glucagon secretion is inhibited by?
high blood glucose, free fatty acids and ketones
Suppression of glucagon secretion is blunted with prolonged _______ (diabetes)
hyperglycemia
Glucagon Stimulatory Effects of liver
Gluconeogenesis
Glycogenolysis
Glucagon Stimulatory Effects of adipose tissue
Lipolysis, free fatty acid release
Glucagon Stimulatory Effects of skeletal muscle
Protein degradation (supply amino acids for gluconeogenesis by liver)
Glycogenolysis
First-phase insulin release is rapidly triggered in response to __________, lasts ~10 minutes (composed of preformed insulin)
increased blood glucose levels
Second-phase insulin release is composed of ______, continues after first-phase and peaks in 1 to 3 hours (depending on glucose load)
newly formed insulin
First-phase insulin release inhibits ______ secretion
glucagon
what may be the earliest detectable beta cell defect predicting onset of type2 diabetes?
Reduced first-phase insulin release
____ and ____ secretion occur incrementally to maintain blood glucose within narrow limits
Insulin and glucagon
what are incretins?
GI hormones that regulate glucose metabolism by effects on insulin and glucagon secretion, tissue insulin sensitivity, and nutrient absorption rate
These hormones are released when food enters the GI tract, referred to as the “incretin effect”
incretins
Gastric inhibitory polypeptide (GIP) secreted by____ of the proximal duodenum epithelium
K cells
Gastric inhibitory polypeptide (GIP) Secretion is stimulated by ?
food entering from stomach
what doesGastric inhibitory polypeptide (GIP) stimulate?
Insulin secretion
Insulin sensitivity
Fatty acid synthesis (liver) and triglyceride synthesis (liver, adipose)
what does Gastric inhibitory polypeptide (GIP) inhibit?
gastric acid secretion
what in Gastric inhibitory polypeptide (GIP) Degraded by?
dipeptidyl peptidase 4 (DPP-4), a circulating enzyme made by adipose (an “adipokine”)
GIP t½ =___ minutes
1-2 minutes
what is Released from distal ileum and colon L-cells within minutes of oral food intake?
Glucagon-like peptide-1 (GLP-1)
Glucagon-like peptide-1 (GLP-1) is Released from distal ileum and colon L-cells within minutes of oral food intake, followed by a second response when nutrients contact ____.
L-cells
Glucagon-like peptide-1 (GLP-1) Secretion stimulated by ____.
oral food intake
Glucagon-like peptide-1 (GLP-1) Stimulates
2 things
Insulin release
Insulin sensitivity
Glucagon-like peptide-1 (GLP-1) inhibits (3 things)
Glucagon secretion
Hepatic gluconeogenesis
Gastric emptying
Glucagon-like peptide-1 is degraded by what?
dipeptidyl peptidase 4 (DPP-4)
An autoimmune disease characterized by pancreatic β-cell destruction and an absolute deficiency of insulin
Type 1 Diabetes Mellitus
Type 1 Diabetes Mellitus Genetic factors
Susceptibility loci: HLA locus contributes up to 50% of risk:
90-95% of Caucasians with type 1 DM have HLA-DR3 or DR4 haplotype (vs 40% without type 1 DM)
40-50% are combined DR3/DR4 heterozygotes (vs 5% without type 1 DM)
Type 1 Diabetes Mellitus Environmental factors
Certain viral infections may be involved in triggering islet cell destruction:
Mumps, rubella, coxsackie B, or cytomegalovirus, among others
Type 1 Diabetes Mellitus Proposed mechanisms for initial immune response
- “Bystander” damage: Viral infections induce islet injury and inflammation, leading to the release of “sequestered” β-cell antigens and the activation of autoreactive T cells (e.g., post-traumatic uveitis)
- “Molecular mimicry”: Viruses may produce proteins that mimic β-cell antigens, trigger autoimmune response (e.g., rheumatic fever)
autoimmune disease associated with the absolute deficiency of insulin
Type 1 Diabetes Mellitus
