‘Sensing’ the link between type 1 and type 2 diabetes

Abstract

Obesity-associated insulin resistance is a core element of metabolic syndrome and type 2 diabetes (T2D). Notably, insulin resistance is also a feature of type 1 diabetes (T1D), where findings in the non-obese diabetic mouse model have implicated transient receptor potential vanilloid-1 (TRPV1+) sensory neurons in local islet inflammation and glucose metabolism. Here, we briefly review the role of TRPV1 in non-obese diabetic (NOD) T1D pathogenesis, highlighting commonalities that suggest TRPV1 may contribute to obesity and T2D as well. With the recently discovered importance of adipose infiltrating lymphocytes in the metabolic disturbances of obesity and T2D, sensory innervation of fat may thus play an analogous role to sensory neurons in the islet--modulating neuroendocrine homeostasis and inflammation. In such a scenario, TRPV1+ sensory nerves would provide the pathoaetiological link connecting the shared metabolic and immunologic features of type 1 diabetes and T2D.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…In the mouse, neurogenic inflammation is clearly involved in maintaining islet inflammation ("insulitis") and b cell death. With the recently recognized importance of adipose tissueinfiltrating lymphocytes in T2DM, it was postulated that sensory innervation of the fat may play an analogous role to pancreatic afferents (see Tsui et al, 2011). This unifying neuroimmune model blurs the line between T1DM and T2DM and places TRPV1 in a central position in the pharmacotherapy of both (see Tsui et al, 2007Tsui et al, , 2011Suri and Szallasi, 2008).…”

“…With the recently recognized importance of adipose tissueinfiltrating lymphocytes in T2DM, it was postulated that sensory innervation of the fat may play an analogous role to pancreatic afferents (see Tsui et al, 2011). This unifying neuroimmune model blurs the line between T1DM and T2DM and places TRPV1 in a central position in the pharmacotherapy of both (see Tsui et al, 2007Tsui et al, , 2011Suri and Szallasi, 2008). Moreover, a number of functional TRP channels were shown to be expressed on pancreatic b cells in which they are believed to play a key role in the regulation of insulin secretion, opening up new avenues for the development of novel antidiabetic drugs (see Colsoul et al, 2011Colsoul et al, , 2013.…”

“…In rodent models of T2DM, there is increasing evidence to imply an important, multifaceted role for TRPV1 in the development and maintenance of insulin resistance (see Suri and Szallasi, 2008;Tsui et al, 2011;Zsombok, 2013). Trpv1(2/2) mice are resistant to diet-induced obesity and associated impaired glucose tolerance (Motter and Ahern, 2008), at least when they grow older (Wanner et al, 2011).…”

Type 1 and type 2 diabetes mellitus: are they mutually exclusive?

“…Due to the existence of these overlap cases, the traditional classification of DM is now questioned, and the two types of DM are proposed to be merely two ends of a continuous spectrum. (3) There are reports of insulin resistance in patients who have apparent T1DM, (4,5) and T2DM are shown in Table I. Of the 125 patients, 11…”

“…Due to the existence of these overlap cases, the traditional classification of DM is now questioned, and the two types of DM are proposed to be merely two ends of a continuous spectrum. (3) There are reports of insulin resistance in patients who have apparent T1DM, (4,5) and classical type 1 autoantibodies have been detected in obese patients who phenotypically have T2DM. (6,7) These reports have led us to hypothesise that there is an overlap in the spectra of the two classical types of DM.…”