Beta cell downregulation?

[Bonaparte]

Short answer: no. High doses of insulin (and concurrent use of shitloads of carbs) will contribute to insulin resistance (bear in mind that AAS decrease insulin resistance, so they largely balance each other out), but there is no reason why it would negatively affect the pancreas.

[Bonaparte]

Short answer: no. High doses of insulin (and concurrent use of shitloads of carbs) will contribute to insulin resistance (bear in mind that AAS decrease insulin resistance, so they largely balance each other out), but there is no reason why it would negatively affect the pancreas.

And it's not like one's pancreas stops producing insulin just because they are using insulin for BB'ing purposes. We only take one or two doses daily of fast-acting insulin, so there is still plenty of opportunity for the pancreas to secrete insulin.

[Splifton]

And it's not like one's pancreas stops producing insulin just because they are using insulin for BB'ing purposes. We only take one or two doses daily of fast-acting insulin, so there is still plenty of opportunity for the pancreas to secrete insulin.

Appreciate the response. I presumed that its secretion and receptor activity would be comparable to the negative feedback mechanism associated with endocrine regulation considering its an internal endocrine organ as well as an exocrine digestive gland. You mentioned one or two doses daily, so the total dosing of exogenous administration is minuscule in comparison to the body's endogenous total secretion in a given day considering the variables are static for ease of measurement?

I wish I could post some of the studies that led me to that presumption. Here is the abstract if it offers any sort of insight in my original connections. I have it in PDF.

Oxidative stress: the vulnerable β-cell

Sigurd Lenzen1 Institute of Clinical Biochemistry, Hannover Medical School, 30625 Hannover, Germany

Antioxidative defence mechanisms of pancreatic β-cells are particularly weak and can be overwhelmed by redox imbalance arising from overproduction of reactive oxygen and reactive nitrogen species. The consequences of this redox imbalance are lipid peroxidation, oxidation of proteins, DNA damage and interference of reactive species with signal transduction pathways, which contribute significantly to βcell dysfunction and death in Type 1 and Type 2 diabetes mellitus. Reactive oxygen species, superoxide radicals (O2•−), hydrogen peroxide (H2O2) and, in a final iron-catalysed reaction step, the most reactive and toxic hydroxyl radicals (OH•) are produced during both pro-inflammatory cytokine-mediated β-cell attack in Type 1 diabetes and glucolipotoxicity-mediated β-cell dysfunction in Type 2 diabetes. In combination with NO•, which is toxic in itself, as well as through its reaction with the O2•− and subsequent formation of peroxynitrite,reactivespeciesplayacentralroleinβ-celldeathduringthedeteriorationofglucosetolerance in the development of diabetes.

[Splifton]

here are two mechanisms for reduction in the level of cell surface insulin receptors by exposure to insulin.

-The first is receptor internalization.

- Surface insulin-receptor complexes are internalized by endocytosis.
Insulin is degraded in lysosomes while 90% of the receptors escape degradation
and recycle to the cell surface by exocytosis.
Since many of the receptors are transferred, transiently, to the various intracellular organelles involved in receptor recycling, fewer remain on the cell surface.

-The second mechanism is receptor degradation.

-Upon prolonged exposure to insulin, endocytosis and recycling of insulin receptors occurs continuously.
During each cycle of endocytosis a small portion (less than 10%) of the internalized receptors are degraded.
After several hours of endocytosis, the total number of insulin receptors is reduced substantially.


^from a lecture^


Attachment 159395


So increasing the possibility of receptor internalization or the prevalence of oxidative stress towards beta cells still wouldn't have a marginal negative effect on the pancreas' future functionality?