ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 EP66 | DOI: 10.1530/endoabs.63.EP66

Whole-body insulin resistance (WBIR) evolving in four stages and its evolutionary effect on the body weight

Song Jae Lee1, Whanwoo Kim1 & Sang Won Shin2

1Chungnam National University, Daejeon, Republic of Korea; 2Korea University, Seoul, Republic of Korea.

Insulin resistance (IR) may be defined as the physiological condition, in which insulin signaling is somehow deranged somewhat irreversibly such that insulin is of little use to cells or tissues. Specific roles of insulin are quite different in the muscle tissue, adipose tissue, and liver. Accordingly, detailed aspects of IR would be very tissue-specific. Meanwhile, IR may develop first in the muscle tissue with a relatively low cell turnover and then progress, in sequence, to the subcutaneous adipose tissue, to the visceral adipose, and to the liver with higher cell turnovers. The cells in a tissue with a lower cell turnover would be exposed longer in average to potential IR-inducing agents and therefore more readily develop IR. Given that IR can hardly be considered a global parameter, it would be essential to subdivide IR into tissue-specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s-AIR), visceral adipose insulin resistance (v-AIR), and hepatic insulin resistance (HIR). Sequential development of tissue-specific IRs, producing tissue-specific metabolic disruptions, would amount to nothing but the whole-body insulin resistance (WBIR) evolving in four main insulin-resistant stages denoted by IR-I, IR-II, IR-III, IR-IV, respectively. WBIR evolution starts with development of MIR (in the IR-I stage), which would effectively enhance adipose glucose uptake and adipose de novo lipogenesis (ADNL), thereby contributing to rapid weight gain; and then advances to the IR-II stage with additional development of s-AIR, which would effectively enhance visceral adipose glucose uptake and v-ADNL, thereby contributing to visceral obesity; and then advances to the IR-III stage with additional development of v-AIR, which would let the visceral adipose tissue as well undergo uninhibited lipolysis, thereby leading to rapid weight loss; and then advances to the IR-IV stage with additional development of HIR, which would let the liver undergo unsuppressed hepatic glucose generation (HGP), thereby elevating severely even the fasting hyperglycemia for eventual diagnosis of diabetes. In conclusion, particularly the effect of WBIR evolution on the body weight largely refutes the entrenched notion of the so-called lipid-induced insulin resistance (LIIR). Instead, the finding that the time-averaged plasma glucose (PG) elevates steadily with WBIR evolution suggests that hyperglycemia itself has an effect of inducing as well as enhancing IR in a vicious cycle.

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