Week 4B: Histopathology Pancreas, Regulation Gene Expression, Nuclear Hormone Receptors & Iron Metabolism Flashcards
HC27-29
Keratin in skin
-Subaceous glands (talgklieren)
-Epithelium cells (plaveisel)
-Hair follicles
-Sweat glands
From which germ later are the endocrine cells of the pancreas (islets) derived?
Endoderm
Secretion in pancreas
-Exocrine: to lumen duodenum through duct
-Endocrine: give hormones to blood
Formation pancreas out of endoderm
Pancreas is a bulge (uitstulping) of primary endoderm tube, but contact with for islets outside world was lost during embryogenesis.
> can differentiate back
> Islets are epithelial cells
HE staining acini of exocrine pancreas: blue on basal cytoplasm (nucleic acids) and red on apical side (protein)
Mitochondrial DNA but a lot of ribosomes with rRNA at basal cytoplasm for production of enzymes
> made as zymogens
Enzyme production in pancreas types
-Zymogens like trypsinogen
-Active enzymes like lipase (needs cofactor, not immediately active), alpha-amylase
Pancreatic ductal epithelium make a lot of water and bicarbonate, why?
To rise the pH from incoming acidic food in duodenum (neutralize)
> apical granules for secretion
How well are islets vascularized compared to exocrine pancreas?
not very distinct
> portal vein structure of blood flow in pancreas
> oxygen use of one part influences potential to use oxygen for downstream part
The best vascularized endocrine pancreatic cells are the
beta cells
Why gap junctions in islets of Langerhans?
Connects cytoplasms
> calcium waves released upon increased ATP/ADP ratio > processing glucose through GLUT2 increases insulin secretion through gap junction. > quick transduction signals
Protects cells against symptoms diabetes mellitus
- sensitive cells
Functions tight junctions
Sorting proteins to PM, and regulate permeability of epithelium (diffusion barrier)
Streptozotocine can target endocrine pancreatic cells, how?
Partly glucose analog > through GLUT2
Has nitrosurea group (urea connected to nitroso group (R-NO) > DNA alkylating agent > toxic for DNA
> also: depletion NAD+ and oxidative stress
> damaged beta cells > autoantibodies
> DM in mice
> ratio alpha/beta cells to 50/50 from 5/95 in healthy
> beta cells affected: take up glucose
Are there active beta cells in DM?
Yes, but DM has threshold vale
Measuring insulin production
C-peptide levels
> insulin made as large pro-hormone by pancreas
> Oxidation of the large C-peptide > 2 intra chain disulfide bonds formed and one exra intra chain linkage disulfide (disulfide bonds in the mature insulin (A and B chains) > hydrogen peroxide made > oxidative stress when too much
Insulomas make much
insulin
Do insulomas of alpha cells exist
yes
Interactions that regulate secretion of insulin an and glucagon
-Plasma glucose
-Neurons > synaptophysin (neuroendocrine cells)
-Autonomous regulation of islets in neuronal
Beta cells take up glucose through GLUT2 and make insulin to inhibit the cAMP and PKA signaling in alpha cells to secrete glucagon release. Other regulations
-Parasympatic neurons can activate it (activated through glucose)
-Adrenaline can bind beta-adrenergic regulation: stimulate glucagon secretion
-Pancreatic islet delta cells take up glucose through GLUT1,3 and insulin binding by SGLT2 > Somatostatin binds receptor on alpha cells: inhibit cAMP and glucagon secretion.
-Glucose uptake through GLUT1/3 by alpha cells
Epsilon cells of pancreas make the hunger hormone:
Ghrelin
Stages of T1DM
1: beta cell autoimmunity but still normoglycemia and presymptomatic
2: dysglucermia and presymptomatic
3: symptomatic
Pancreatitis
exocrine pancreas damaged: autoinflammation
> islets not targeted
HC28: Hierarchy of metabolic regulation
Top down >
- Transcription-translation
- Expression isozymes or isotypes
- Protein synthesis/breakdown
- Proteolytic activation
- PTMs like phosphorylation
- Allosteric control by metabolites
< Bottom up
Regulating steps gene expression
-Transcriptional control
-RNA processing control
-RNA transport control
-Translation control protein activity control
Gene expression profiles reflect:
Function of organs
like exretion digestive enzymes by pancreas and lipid transport by liver