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Upon stress, corticotropin-releasing factor is released from the hypothalamus, which leads to adrenocorticotropic hormone release from the pituitary which stimulates the production of glucocorticoids (cortisol in human and corticosterone in rodents) in the adrenal gland

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The decrease in A1c induced by metformin is independent of age, weight, and diabetes duration as long as some residual -cell function remains (22)

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Oral or topical versions probably dont need to be kept at such low temperatures but should at least be kept in a cool, dry environment