Cyproheptadine - Leads To Diabetes?

[ecstatichamster]

there are a number of studies like these. Dosages were high. Many were tissue (in vitro) and not in live animals. But still...maybe this accounts for Cypro causing weight gain...


MECHANISM BY WHICH CYPROHEPTADINE INHIBITS INSULIN SECRETION

• 1Isolated islets of Langerhans from the rat have been used in studies designed to elucidate the mechanism by which cyproheptadine inhibits insulin secretion.
• 2d-Glucose and tolbutamide, both of which require extracellular Ca2+ to produce insulin release, failed to evoke a secretory response from islets pretreated with cyproheptadine. Conversely veratridine, the calcium ionophore A23187 and theophylline, all of which are capable of mobilizing sufficient intracellular Ca2+ to evoke insulin secretion in the absence of extracellular Ca2+, produced similar responses from cyproheptadine pretreated and control islets.
• 3Cyproheptadine completely inhibited Ca2+ uptake induced by d-glucose and high K+o, two agents which depolarize the islet β-cell membrane, whilst Ca2+ uptake elicited by removal of extracellular Na+ (i.e. Na+-Ca2+ counter transport) was only slightly reduced.
• 4A significant increase in Na+ uptake produced by veratridine was sensitive to tetrodoxin but only partially reduced by cyproheptadine.
• 5These results suggest that cyproheptadine inhibits depolarization-dependent calcium entry into pancreatic β-cells.

And this one:
http://www.sciencedirect.com/science/article/pii/0006295277900119

Experiments were conducted to determine whether the reduced pancreatic insulin content in rats treated with cyproheptadine is due to a drug-induced inhibition in insulin biosynthesis. Pancreatic islets were isolated six hours after the last of eight daily oral doses of cyproheptadine (45 mgkg) or water (control). Islets from drug-treated animals were depleted of insulin and exhibited a significant hyperplasia. Addition of cyproheptadine in vitro to islets from drug-treated and control animals caused an inhibition of proinsulin synthesis, as measured by 3H-leucine incorporation. The degree of inhibition was dependent on drug concentration and at 8 × 10−5 M the incorporation of label into proinsulin was completely prevented. The inhibitory effects of cyproheptadine were less pronounced when incorporation of label into total islet protein was measured. The drug was apparently less effective in altering the synthesis of other islet proteins and showed selectivity for inhibition of proinsulin synthesis. Measurement of proinsulin content in the whole pancreas of rats given cyproheptadine in vivo showed that a 77% reduction occurred by six hours after a single 45 mgkg oral dose. The results indicate that an inhibition of proinsulin synthesis is responsible for the depletion of pancreatic insulin in rats given cyproheptadine.

And this more recent study:


Inhibition of Insulin Synthesis by Cyproheptadine: Effects on Translation 1Present address: U.S. Environmental Protection Agency, Ariel Rios Building—2842T, 1200 Pennsylvania Ave., N.W., Washington, DC 20460. | Toxicological Sciences | Oxford Academic

The diabetogenic compound cyproheptadine (CPH) is known to inhibit insulin synthesis and deplete rat pancreatic insulin content in intact animals, isolated pancreatic islets, and in clonal insulin-producing cells (Chow et al., 1990; Halban et al., 1979; Hintze et al., 1977b; Miller and Fischer, 1990; Rickert et al., 1975). The clonal insulin-producing cell line, RINm5F, has been extensively studied and has been shown to be a valid model for investigations into the mechanisms of CPH-induced β-cell toxicity (Miller and Fischer, 1990; Miller et al., 1993). The inhibition of insulin synthesis in response to CPH treatment in RINm5F cells has been shown to occur without a commensurate decline in preproinsulin mRNA (PPImRNA) levels (Miller et al., 1993), suggesting that the CPH-induced inhibition of insulin synthesis may be due to one or more post-transcriptional mechanisms. The goal of the present study was to produce direct evidence of CPH effects on the translation process, an action not previously reported for chemicals known to alter the function of insulin producing cells.

CPH is a member of a group of structurally related, heterocyclic, nitrogen-containing compounds known to produce morphologic and biochemical changes in insulin-producing cells in vivo and in vitro (Hintze et al., 1977a,b;Miller et al., 1993). Certain CPH analogs are much more potent than the parent compound while other structural analogs have no effect on insulin synthesis because they lack the minimum chemical structure necessary for CPH-like toxicity (Hintze et al., 1977a). Two well-characterized structural analogs of CPH are 4-diphenylmethylpiperidine (4-DPMP) and 2-diphenylmethylpiperidine (2-DPMP); 4-DPMP has been shown to produce CPH-like β-cell toxicity while 2-DPMP elicits no toxicological effects (Hintze et al., 1977a; Miller et al., 1993). Current studies employing CPH and these analogs were undertaken to determine if the effects of CPH-like compounds on the subcellular location of PPImRNA exhibit the same requirements for chemical structure as previously reported for CPH-induced pancreatic β-cell toxicity.[/quote]

 

[Sucrates]

I've taken cypro for weeks or months concurrently a number of times and I've only seen weight gain when calories were increased.

 

[LukeL]

Bump

 

[haidut]

there are a number of studies like these. Dosages were high. Many were tissue (in vitro) and not in live animals. But still...maybe this accounts for Cypro causing weight gain...


MECHANISM BY WHICH CYPROHEPTADINE INHIBITS INSULIN SECRETION


And this one:
http://www.sciencedirect.com/science/article/pii/0006295277900119



And this more recent study:


Inhibition of Insulin Synthesis by Cyproheptadine: Effects on Translation 1Present address: U.S. Environmental Protection Agency, Ariel Rios Building—2842T, 1200 Pennsylvania Ave., N.W., Washington, DC 20460. | Toxicological Sciences | Oxford Academic

Decreasing insulin is not bad thing. In fact, cyproheptadine has also been used to treat diabetes. If the cells can metabolize glucose properly, not much insulin release is needed. In fact, potassium is responsible for most of the glucose update in the cell that people normally ascribe to insulin. And if the cell can absorb the glucose with much less insulin then this is a very beneficial effect of cypro. For comparison, glycine has the same effect - i.e. lower both glucose and insulin release, as it sensitizes the cells to insulin and stimulates glucose uptake and metabolism through non-insulin pathways.
Glycemia, starch, and sugar in context
"...Insulin is important in the regulation of blood sugar, but its importance has been exaggerated because of the diabetes/insulin industry. Insulin itself has been found to account for only about 8% of the "insulin-like activity" of the blood, with potassium being probably the largest factor. There probably isn't any process in the body that doesn't potentially affect blood sugar."

The metabolic response to ingested glycine

 

[paymanz]

Weight gain is caused by increasement of appetite I believe,at least mostly it is.

 

[Soren]

Decreasing insulin is not bad thing. In fact, cyproheptadine has also been used to treat diabetes. If the cells can metabolize glucose properly, not much insulin release is needed. In fact, potassium is responsible for most of the glucose update in the cell that people normally ascribe to insulin. And if the cell can absorb the glucose with much less insulin then this is a very beneficial effect of cypro. For comparison, glycine has the same effect - i.e. lower both glucose and insulin release, as it sensitizes the cells to insulin and stimulates glucose uptake and metabolism through non-insulin pathways.
Glycemia, starch, and sugar in context
"...Insulin is important in the regulation of blood sugar, but its importance has been exaggerated because of the diabetes/insulin industry. Insulin itself has been found to account for only about 8% of the "insulin-like activity" of the blood, with potassium being probably the largest factor. There probably isn't any process in the body that doesn't potentially affect blood sugar."

The metabolic response to ingested glycine

Would this mean that theoretically that type 1 diabetics would not need to inject insulin if they increased their potassium intake and took care of things such as cortisol, Glucagon etc?

I'm assuming that for type 1 diabetics some insulin is still needed?

 

[haidut]

Would this mean that theoretically that type 1 diabetics would not need to inject insulin if they increased their potassium intake and took care of things such as cortisol, Glucagon etc?

I'm assuming that for type 1 diabetics some insulin is still needed?

Older studies by Selye and St. Gyorgyi showed that potassium and succinic acid lowered blood glucose even in people with severe type I diabetes. I don't know about needed doses but in general niacinamide, aspirin and anything that lower lipolysis (sugar) should help the pancreas regenerate.