Hepatalin: the missing link in prediabetes, obesity, and type 2 diabetes.

Hepatalin is a hormone secreted by the liver in response to pulses of insulin after a mixed nutrient meal, but only if the liver receives two permissive synergistic feeding signals from the stomach. Hepatalin stimulates glucose uptake and storage as glycogen in skeletal muscle, heart, and kidney but not liver, intestines, or adipocytes. Insulin acts primarily on liver and fat.

An animal model of gestational obesity and prediabetes: HISS-dependent insulin resistance induced by a high-sucrose diet in Sprague Dawley rats.

This study developed an animal model of gestational obesity and prediabetes in Sprague Dawley rats using 35% sucrose supplementation (SS). Postprandially, insulin stimulates glucose uptake and nutrient partitioning via insulin-dependent action as well as hepatic insulin sensitizing substance (HISS) - dependent action. HISS is glycogenic in heart, kidney, and skeletal muscle (contrasting insulin's lipogenic actions in liver and adipose tissue) and is responsible for the vasodilatory action of insulin.

Gestational postprandial insulin sensitivity in the Sprague Dawley rat: the putative role of hepatic insulin sensitizing substance in glucose partitioning in pregnancy.

Pregnancy requires adaptation of maternal insulin sensitivity. In the fed state, a pulse of insulin stimulates glucose uptake and nutrient energy storage via insulin-dependent as well as hepatic insulin sensitizing substance (HISS)-dependent action. HISS is released by the liver in the fed state in the presence of signals integrated through the liver and a pulse of insulin.

Postprandial insulin action relies on meal composition and hepatic parasympathetics: dependency on glucose and amino acids: Meal, parasympathetics & insulin action.

Insulin sensitivity (IS) increases following a meal. Meal composition affects postprandial glucose disposal but still remains unclear which nutrients and mechanisms are involved. We hypothesized that gut-absorbed glucose and amino acids stimulate hepatic parasympathetic nerves, potentiating insulin action.

Acute glucagon induces postprandial peripheral insulin resistance.

Glucagon levels are often moderately elevated in diabetes. It is known that glucagon leads to a decrease in hepatic glutathione (GSH) synthesis that in turn is associated with decreased postprandial insulin sensitivity. Given that cAMP pathway controls GSH levels we tested whether insulin sensitivity decreases after intraportal (ipv) administration of a cAMP analog (DBcAMP), and investigated whether glucagon promotes insulin resistance through decreasing hepatic GSH levels.