Diuresis and α-glucosidase inhibition by erythritol in Aedes aegypti (Diptera: Culicidae) and viability for efficacy against mosquitoes.

BACKGROUND: Sugar alcohols, such as erythritol, are low-impact candidates for attractive toxic sugar baits (ATSB) to kill mosquitoes. To determine whether erythritol has a viable future in ATSB formulations, a suite of assays was conducted to diagnose toxicity mechanisms and starvation effects on mortality in Aedes aegypti (L.) as a model system. METHODS: We measured general carbohydrate load, glucosidase levels, and free glucose in intoxicated adult mosquitoes to observe whether sugar digestion was impaired. We assayed the effects of sugar combinations with erythritol on larvae and adults. To measure erythritol effects when mosquitoes were not resource-deprived, additional assays manipulated the prior starvation status. RESULTS: Up to 50,000 ppm of erythritol in water had no effect on larvae within 72 h, but an ammonia spike indicated diuresis in larvae as early as 4 h (F8,44 = 22.50, P < 0.0001) after sucrose/erythritol combinations were added. Adult consumption of erythritol was diuretic regardless of the sugar pairing, while sucrose and erythritol together generated above 80% mortality (F2,273 = 33.30, P < 0.0001) alongside triple the normal excretion (F5,78 = 26.80, P < 0.0004). Glucose and fructose paired individually with erythritol had less mortality, but still double the fecal excretion. When ingesting erythritol-laced meals, less sugar was detected in mosquitoes as compared to after sucrose meals (χ2 = 12.54, df = 1, P = 0.0004). CONCLUSIONS: Data showed that erythritol is a linear competitive inhibitor of α-glucosidase, marking it as a novel class of insecticide in the current research climate. However, the efficacy on larvae was null and not persistent in adult mosquitoes when compared across various starvation levels. Despite significant diuresis, the combined effects from erythritol are not acute enough for vector control programs considering ATSB against mosquitoes.

Fatally impaired glucose digestion by propylene glycol in Aedes aegypti (Diptera: Culicidae) and co-formulation with terpenoids for enhancing attractive toxic sugar baits.

Propylene glycol (PG) demonstrates greater efficacy than other sugar polyols. However, the attributes it confers for toxicity and possible co-formulation with other ingredients are unknown. To evaluate this, α-glucosidase and glucose oxidase reactions were performed in Aedes aegypti (L.) (Diptera: Culicidae) to categorize if PG behaves similarly to prior studied sugar alcohols. A combination of no-choice and choice assays was used to determine effective ratios of PG and sucrose, competitiveness against a control of 10% sucrose, and whether mosquitoes recovered from PG consumption. The final trials included ß-cyclodextrin encapsulated cinnamon leaf oil, clove stem oil, patchouli oil, garlic oil, cedarwood oil, and papaya seed oil formulated with 5% sucrose + 5% PG. PG functioned as a linear competitive inhibitor of α-glucosidase. The efficacy of PG was synergized by co-ingestion with equivalent ratios of sucrose. Unlike the high diuretic response to other sugar alcohols, PG resulted in diminished excretion regardless of being co-formulated with sucrose or terpenoids. PG is not especially competitive against unadulterated sugar meals but is likewise not clearly repellent. Although mosquitoes did not recover from ingestion of the glycol meals, there was no indication that mortality would continue to accumulate once the treatments were removed. Of the terpenoids tested, cinnamon and patchouli caused ~50% or less mortality; garlic, cedarwood, and clove caused 80-90% mortality; and papaya seed caused 100% mortality, exceeding all other test groups and the formulation blank. PG is a useful supporting ingredient in attractive toxic sugar bait formulations with flexibility in formulation.

Astrocyte Glycogen Is a Major Source of Hypothalamic Lactate in Rats With Recurrent Hypoglycemia.

Lactate is an important metabolic substrate for sustaining brain energy requirements when glucose supplies are limited. Recurring exposure to hypoglycemia (RH) raises lactate levels in the ventromedial hypothalamus (VMH), which contributes to counterregulatory failure. However, the source of this lactate remains unclear. The current study investigates whether astrocytic glycogen serves as the major source of lactate in the VMH of RH rats. By decreasing the expression of a key lactate transporter in VMH astrocytes of RH rats, we reduced extracellular lactate concentrations, suggesting excess lactate was locally produced from astrocytes. To determine whether astrocytic glycogen serves as the major source of lactate, we chronically delivered either artificial extracellular fluid or 1,4-dideoxy-1,4-imino-d-arabinitol to inhibit glycogen turnover in the VMH of RH animals. Inhibiting glycogen turnover in RH animals prevented the rise in VMH lactate and the development of counterregulatory failure. Lastly, we noted that RH led to an increase in glycogen shunt activity in response to hypoglycemia and elevated glycogen phosphorylase activity in the hours following a bout of hypoglycemia. Our data suggest that dysregulation of astrocytic glycogen metabolism following RH may be responsible, at least in part, for the rise in VMH lactate levels. ARTICLE HIGHLIGHTS: Astrocytic glycogen serves as the major source of elevated lactate levels in the ventromedial hypothalamus (VMH) of animals exposed to recurring episodes of hypoglycemia. Antecedent hypoglycemia alters VMH glycogen turnover. Antecedent exposure to hypoglycemia enhances glycogen shunt activity in the VMH during subsequent bouts of hypoglycemia. In the immediate hours following a bout of hypoglycemia, sustained elevations in glycogen phosphorylase activity in the VMH of recurrently hypoglycemic animals contribute to sustained elevations in local lactate levels.