In VivoInsulin-Dependent Glucose Uptake of Specific Tissues Is Decreased during Aging of Mature Wistar Rats¹

Abstract

Aging has been associated with peripheral insulin resistance in both humans and rats. However, the specific tissues that become insensitive to insulin before glucose homeostasis is altered remain to be elucidated. In the present work we studied the glucose metabolic index of a number of tissues known to be insulin sensitive in 3-and 24-month-old Wistar rats by measuring 2-deoxy-D-[1-3 H]glucose uptake both under euglycemic-hyperinsulinemic conditions and in the basal state. Analysis of the glucose infusion rate to maintain normoglycemia during the clamp confirmed that the old rats show overall insulin resistance at both saturating and subsaturating insulin concentrations. The maximal response of glucose uptake to insulin as well as insulin sensitivity in red and white quadriceps were unaltered in old rats. In contrast, glucose uptake by soleus and diaphragm was poorly stimulated in old animals, and a marked decrease in insulin sensitivity was observed in both tissues. In heart, only the sensitivity to the hormone, not the maximal response, was impaired in old rats. In white adipose tissue, no significant stimulation was detected. We conclude that during aging in Wistar rats and before fasting plasma insulin and glucose levels become altered, specific tissues develop insulin resistance, whereas other remain insulin sensitive. We postulate that fat tissue plays a qualitative important role in eliciting the insulin resistance in old animals. Due to the metabolic characteristics of the aged Wistar rat, the changes reported might reflect what occurs in nonobese elderly humans, nongenetically committed to develop type 2 diabetes. (Endocrinology 138: 49 -54, 1997)

Vanadate fully stimulates insulin receptor substrate‐1 associated phosphatidyl inositol 3‐kinase activity in adipocytes from young and old rats

“…Male adult (3 months; body weight 408±29 g) and old (24 months; body weight 622±22 g) Wistar rats fed ad libitum on a standard laboratory chow and water were used throughout this study. The characteristics of the two groups of rats have been previously reported [24, 25]. Adipocyte size was similar in both groups of animals [25].…”

“…Since vanadate activates PI 3‐kinase and its association to IRS‐1, GLUT‐4 translocation, and 2‐deoxyglucose uptake, it seems interesting to investigate whether it can overcome the insulin insensitivity of these cellular events in insulin‐resistant cells. Therefore, we explored the effect of vanadate in isolated adipocytes from old rats, a cell type previously reported to be very insensitive to insulin [24–26]. As can be seen in Fig.…”

“…In the present work we analyzed the vanadate effect on complex formation between the p85α subunit of PI 3‐kinase and insulin receptor substrate‐1 (IRS‐1), and the PI 3‐kinase activity associated with it, as well as the GLUT‐4 translocation and glucose uptake in isolated adipocytes from 3‐month‐old mature (not juvenile) rats, and explored whether it can stimulate 2‐deoxyglucose uptake in insulin‐resistant adipocytes from 24‐month‐old rats, which we have previously shown to be extremely insulin‐insensitive both in vivo [24]and in vitro [25, 26].…”

Effects of diet supplementation with olive oil and guar upon fructose-induced insulin resistance in normal rats

“…The food intake was measured every other week during 65 days in groups of 4-5 rats and over periods of 3-5 days. After 65 days, a hyperinsulinemiceuglycemic clamp [31] was performed over 90 min in rats in overnight starved condition. For such a purpose, rats were anaesthetized with pentobarbital administered intraperitoneally (60 lg per g body wt.…”

Broccoli Sprouts Promote Sex-Dependent Cardiometabolic Health and Longevity in Long-Evans Rats

“…In contrast, only male BrSp-fed rats exhibited improved fasting glucose levels despite no differences in body composition, which is consistent with other reports in male rats using sulforaphane [ 1 ], and underscores that body composition is by no means the sole determinant of glucose homeostasis. This is perhaps best exemplified by the observation that among all groups over time, fasting glucose levels as well as GTT and ITT AUCs remained largely unchanged (or even decreased), despite increases in body weight and fat deposition, which has been reported by others [ 24 , 25 , 26 ].…”