We tested the hypothesis that K(+) intake is sensed by putative K(+) sensors in the splanchnic areas, and renal K(+) handling is regulated by this signal. K(+) was infused for 2 h into overnight-fasted rats via the jugular vein (systemic infusion), hepatic portal vein (intraportal infusion), or stomach (intragastric infusion) (n = 5 each), and plasma K(+) concentration ([K(+)]) and renal K(+) excretion were measured during the 2-h preinfusion, 2-h K(+) infusion, and 3-h washout periods. During systemic K(+) infusion, plasma [K(+)] increased by approximately 1.3 mM (P < 0.05), and, on cessation of the K(+) infusion, plasma [K(+)] fell to the preinfusion level within 1-2 h. Renal K(+) excretion changed in proportion to the changes in plasma [K(+)]. During intraportal or intragastric K(+) infusion, plasma [K(+)] and renal K(+) excretion profiles were similar to those with systemic infusion. The effects of K(+) infusions via the different routes (n = 5 or 6 each) were also studied during simultaneous feeding of overnight-fasted rats with a K(+)-deficient diet. During the meal, intraportal infusion resulted in increases in plasma [K(+)] similar to those with the systemic K(+) infusion, while intragastric K(+) infusion did not significantly increase plasma [K(+)]. Thus, when the intragastric K(+) infusion was combined with a meal, there was marked enhancement of clearance of the K(+) infused, which was associated with an apparent increase in renal efficiency of K(+) excretion. These data suggest that there may be a gut factor that enhances renal efficiency of K(+) excretion during meal (or dietary K(+)) intake.

Insulin stimulates both glucose and K؉ uptake, and high-fat feeding is known to decrease insulin-stimulated glucose uptake. The purpose of this study was to examine whether insulin's actions on glucose and K ؉ uptake are similarly decreased by a high-fat diet. Wistar rats were fed a standard control (12.2% fat; n ‫؍‬ 6) or high-fat (66.5% fat; n ‫؍‬ 13) diet for 15 days. Because K ؉ content was 1% in the control and 0.5% in the high-fat diet and because the rats ate less of the high-fat diet, we also compared the high-fat diet with 0.5% K ؉ (HFD; n ‫؍‬ 7) to a high-fat diet supplemented with 1.5% K

To evaluate the role of the hexosamine biosynthesis pathway (HBP) in fat-induced insulin resistance, we examined whether fat-induced insulin resistance is additive to that induced by increased HBP flux via glucosamine infusion and, if so, whether such additive effects correlate with muscle HBP product levels. Prolonged hyperinsulinemic (~550 pmol/l) euglycemic clamps were conducted in conscious overnight-fasted rats. After the initial 150 min to attain steady-state insulin action, rats received an additional infusion of saline, Intralipid, glucosamine, or Intralipid and glucosamine (n = 8 or 9 for each) for 330 min. At the conclusion of clamps, skeletal muscles (soleus, extensor digitorum longus, and tibialis anterior) were taken for the measurement of HBP product levels. Intralipid and glucosamine infusions decreased insulin-stimulated glucose uptake (R d ) by 38 and 28%, respectively. When the infusions were combined, insulin-stimulated R d decreased 47%, significantly more than with Intralipid or glucosamine alone (P < 0.05). The glucosamineinduced insulin resistance was associated with four-to fivefold increases in muscle HBP product levels. In contrast, the Intralipid-induced insulin resistance was accompanied by absolutely no increase in HBP product levels in all of the muscles examined. Also, when infused with glucosamine, Intralipid decreased insulin action below that with glucosamine alone without changing HBP product levels. In a separate study, short-term (50 and 180 min) Intralipid infusion also failed to increase muscle HBP product levels. In conclusion, increased availability of plasma free fatty acids induces peripheral insulin resistance without increasing HBP product levels in skeletal muscle. Diabetes 50:418-424, 2001