Inter-organ insulin-leptin signal crosstalk from the liver enhances survival during food shortages.

Crosstalk among organs/tissues is important for regulating systemic metabolism. Here, we demonstrate inter-organ crosstalk between hepatic insulin and hypothalamic leptin actions, which maintains survival during food shortages. In inducible liver insulin receptor knockout mice, body weight is increased with hyperphagia and decreased energy expenditure, accompanied by increased circulating leptin receptor (LepR) and decreased hypothalamic leptin actions. Additional hepatic LepR deficiency reverses these metabolic phenotypes. Thus, decreased hepatic insulin action suppresses hypothalamic leptin action with increased liver-derived soluble LepR. Human hepatic and circulating LepR levels also correlate negatively with hepatic insulin action indices. In mice, food restriction decreases hepatic insulin action and energy expenditure with increased circulating LepR. Hepatic LepR deficiency increases mortality with enhanced energy expenditure during food restriction. The liver translates metabolic cues regarding energy-deficient status, which is reflected by decreased hepatic insulin action, into soluble LepR, thereby suppressing energy dissipation and assuring survival during food shortages.

A case of slowly progressive type 1 diabetes with insulin independence maintained for 10 years with α-glucosidase inhibitor monotherapy.

Slowly Progressive Type 1 Diabetes (SPT1D) is characterized by the absence of insulin dependence at the onset of diabetes and persistent detection of islet cell autoantibodies. These patients with high titers of glutamic acid decarboxylase autoantibodies (GADA) are known to progress to insulin dependence within several years. Low-dose insulin injections have been reported to prevent or delay the decline of insulin secretion in SPT1D patients. We experienced the case of an SPT1D patient with preserved endogenous insulin secretion and good glycemic control achieved with α-glucosidase inhibitor (α-GI) treatment alone for 10 years despite having continuously elevated GADA titers. The details of this case suggest that α-GI treatment might have preventive effects on SPT1D progression.