Glucoreceptors Located Inside the Blood-Brain Barrier Mediate Hypoglycemia-Induced LH Inhibition in Man

Abstract

Objective: To establish the role of hyperinsulinemia and hypoglycemia during the insulin tolerance test (ITT) in the regulation of luteinizing hormone (LH) secretion and the location with respect to the blood-brain barrier (BBB) of the glucosensitive areas controlling LH release. Methods: The LH-secretory pattern during an ITT (0.15 IU/kg body weight) was evaluated in 8 normal men during infusion with normal saline (control test), glucose or fructose. Results: lnsulin-induced hypoglycemia produced a significant decrement in serum LH levels in the control test, but not when the concomitant infusion of glucose prevented hypoglycemia. Fructose infusion did not change LH decrease during ITT. Conclusions: These data exclude a direct role of hyperinsulinemia in the mechanism underlying the inhibition of LH secretion during ITT. Furthermore, since glucose but not fructose crosses the BBB, the LH decrease during ITT appears to be generated by hypoglycemia at the level of glucosensitive areas located inside the BBB.

Preserved inhibitory effect of recurrent hypoglycaemia on the male gonadotrophic axis

“…This hypothesis is supported by recent data of Coiro et al. , who found that the LH decrease during insulin‐induced hypoglycaemia is generated by glucosensitive areas located inside the blood–brain barrier 30 …”

“…This hypothesis is supported by recent data of Coiro et al, who found that the LH decrease during insulin-induced hypoglycaemia is generated by glucosensitive areas located inside the blood-brain barrier. 30 Finally, the finding of normalized sex hormone levels in the morning of day 2 after two episodes of hypoglycaemia needs to be discussed as it seems to have some clinical relevance for type 1 diabetic patients. A large number of these patients exhibit hypoglycaemic episodes, 31 especially during the night-time, 32,33 which presumably decreases serum LH and testosterone levels.…”

Stress and the Reproductive System

“…Insulin-induced hypoglycemia is a highly quantifiable and reproducible stressor that inhibits LH secretion to which animals, including humans, do not habituate. 173,181,182 In addition to insulin-induced hypoglycemia, acute glucoprivation by 2-deoxyglucose administration profoundly suppresses pulsatile LH secretion in the rat. 107,179,180 Affects on LH pulse amplitude are also reported for the rat 177 and ewe, 178 although not in the monkey.…”

Carbohydrates and feeding: An extension of the glucostatic theory of appetite regulation

“…It was originally suspected that these "glucoreceptors" were located in the CNS and probably in the hypothalamus (Mayer, 1956). As time passed, it was suspected and later demonstrated (Shiota and Magnuson, 2008) that these receptors were in fact located in hepatic circulation (Niijima, 1969;Russek & Grinstein, 1974;Russek, 1981), the gastrointestinal tract (Mei, 1978), the causal hind brain (Ritter, 1981), and more recently the blood brain barrier (BBB) (Coiro, 2004). The decrease or increase in the utilization of glucose described above then in turn stimulates either satiety or hunger respectively along with a variety of other factors.…”