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Glycogenin (GN-1) is essential for the formation of a glycogen granule; however, rarely has it been studied when glycogen concentration changes in exercise and recovery. It is unclear whether GN-1 is degraded or is liberated and exists as apoprotein (apo)-GN-1 (unglycosylated). To examine this, we measured GN-1 protein and mRNA level at rest, at exhaustion (EXH), and during 5 h of recovery in which the rate of glycogen restoration was influenced by carbohydrate (CHO) provision. Ten males cycled (65% V[O.sub.2max]) to volitional EXH (117.8 [+ or -] 4.2 min) on two separate occasions. Subjects were administered carbohydrate (CHO; 1 g x [kg.sup.-1] x [h.sup.-1] Gatorlode) or water [placebo (PL)] during 5 h of recovery. Muscle biopsies were taken at rest, at EXH, and following 30, 60, 120, and 300 min of recovery. At EXH, total glycogen concentration was reduced (P < 0.05). However, GN-1 protein and mRNA content did not change. By 5 h of recovery, glycogen was resynthesized to ~60% of rest in the CHO trial and remained unchanged in the PL trial. GN-1 protein and mRNA level did not increase during recovery in either trial. We observed modest amounts of apo-GN-1 at EXH, suggesting complete degradation of some granules. These data suggest that GN-1 is conserved, possibly as very small, or nascent, granules when glycogen concentration is low. This would provide the ability to rapidly restore glycogen during early recovery. skeletal muscle; carbohydrate; exhaustion; resynthesis; recovery doi:10.1152/ajpendo.00598.2006.

Although acute alkaloid caffeine (CAF) ingestion results in an impaired glucose tolerance, chronic coffee (RCOF) ingestion decreases the risk of developing type 2 diabetes. This study examines the hypothesis that CAF ingestion impairs glucose tolerance to a greater extent than RCOF and that the ingestion of decaffeinated coffee (DECAF) results in a positive effect. Eleven healthy males underwent 4 double-blinded randomized trials. Each trial included the ingestion of either: 1) CAF in capsule form (4.45 mg/kg body weight), 2) RCOF (4.45 mg/kg body weight caffeine), 3) dextrose (placebo, PL) in capsule form, or 4) DECAF (equal in volume to the RCOF trial), followed 1-h later by a 2-h oral glucose tolerance test. Blood samples were collected at baseline (-30), 0 (time of treatment ingestion), 60 (initiation of oral glucose tolerance test), 75, 90, 120, 150, and 180 min. Area under the curve for glucose and insulin were higher (P [less than or equal to] 0.05) following CAF than both PL and DECAF and, although a similar trend (P = 0.07) was observed following RCOF compared with DECAF, the effect was less pronounced. Interestingly, DECAF resulted in a 50% lower glucose response (P [less than or equal to] 0.05) than PL, suggesting that the effects of PL and DECAF on glucose tolerance are not the same. These findings suggest that the effects of CAF and RCOF are not identical and may provide a partial explanation as to why acute CAF ingestion impairs glucose tolerance while chronic RCOF ingestion protects against type 2 diabetes. KEY WORDS: * chlorogenic acids * epinephrine * type 2 diabetes

Glycogenin is the self-glycosylating protein primer that initiates glycogen granule formation. To examine the role of this protein during glycogen resynthesis, eight male subjects exercised to exhaustion on a cycle ergometer at 75% V[O.sub.2max] followed by five 30-s sprints at maximal capacity to further deplete glycogen stores. During recovery, carbohydrate (75 g/h) was supplied to promote rapid glycogen repletion, and muscle biopsies were obtained from the vastus lateralis at 0, 30, 120, and 300 min postexercise. At time 0, no free (deglycosylated) glycogenin was detected in muscle, indicating that all glycogenin was complexed to carbohydrate. Glycogenin activity, a measure of the glycosylating ability of the protein, increased at 30 min and remained elevated for the remainder of the study. Quantitative RT-PCR showed elevated glycogenin mRNA at 120 min followed by increases in protein levels at 300 min. Glycogenin specific activity (glycogenin activity/relative protein content) was also elevated at 120 min. Proglycogen increased at all time points, with the highest rate of resynthesis occurring between 0 and 30 min. In comparison, macroglycogen levels did not significantly increase until 300 min postexercise. Together, these results show that, during recovery from prolonged exhaustive exercise, glycogenin mRNA and protein content and activity increase in muscle. This may facilitate rapid glycogen resynthesis by providing the glycogenin backbone of proglycogen, the major component of glycogen synthesized in early recovery. granule; proglycogen; macroglycogen; recovery; carbohydrate

We determined whether intraportal caffeine infusion, at rates designed to create concentrations similar to that seen with normal dietary intake, would enhance net hepatic glucose uptake (NHGU) during a glucose load. Dogs (n = 15) were implanted with sampling and infusion catheters as well as flow probes >16 d before the studies. After a basal sampling period, dogs were administered a somatostatin infusion (0-150 min) as well as intraportal infusions of glucose [18 [micro]mol/ (kg- min)], basal glucagon [0.5 ng/(kg, min)], and insulin [8.3 pmol/ (kg * min)] to establish mild hyperinsulinemia. Arterial glucose was clamped at 10 mmol/L with a peripheral glucose infusion. At 80 min, either saline (Control; n = 7) or caffeine [1.5 [micro]mol/(kg * min); n = 8] was infused into the portal vein. Arterial insulin, glucagon, norepinephrine, and glucose did not differ between groups. In dogs infused with caffeine, NHGU was significantly higher than in controls [21.2 [+ or -] 4.3 vs. 11.2 [+ or -] 1.6 [micro]mol/(kg * min)]. Caffeine increased net hepatic lactate output compared with controls [12.5 [+ or -] 3.8 vs. 5.5 [+ or -] 1.5 [micro]mol/(kg * min)]. These findings indicate that physiologic circulating levels of caffeine can enhance NHGU during a glucose load, and the added glucose consumed by the liver is in part converted to lactate. KEY WORDS: * glycogen * coffee * carbohydrate * methylxanthines

Caffeine ingestion negatively affects insulin sensitivity during an oral glucose tolerance test (OGTT) in lean and obese men, but this has not been studied in individuals with type 2 diabetes. We examined the effects of caffeine ingestion on insulin and glucose homeostasis in obese men with type 2 diabetes. Men (n = 12) with type 2 diabetes (age = 49 [+ or -] 2 y, BMI = 32 [+ or -] 1 kg/[m.sup.2]) underwent 2 trials, 1 wk apart, in a randomized, double-blind design. Each trial was conducted after withdrawal from caffeine, alcohol, exercise, and oral hypoglycemic agents for 48 h and an overnight fast. Subjects randomly ingested caffeine (5 mg/kg body weight) or placebo capsules and 1 h later began a 3 h 75 g OGTT. Caffeine increased (P < 0.05) serum insulin, proinsulin, and C-peptide concentrations during the OGTT relative to placebo. Insulin area under the curve was 25% greater (P < 0.05) after caffeine than after placebo ingestion. Despite this, blood glucose concentration was also increased (P < 0.01) in the caffeine trial. After caffeine ingestion, blood glucose remained elevated (P < 0.01) at 3 h postglucose load (8.9 [+ or -] 0.7 mmol/L) compared with baseline (6.7 [+ or -] 0.4 mmol/L). The insulin sensitivity index was lower (14%, P = 0.02) after caffeine than after placebo ingestion. Overall, despite elevated and prolonged proinsulin, C-peptide, and insulin responses after caffeine ingestion, blood glucose was also increased, suggesting an acute caffeine-induced impairment in blood glucose management in men with type 2 diabetes. KEY WORDS: * caffeine * carbohydrate * insulin resistance * hyperinsufinemia * insulin sensitivity index

Consumption of large amounts of coffee has been shown to decrease the incidence of type 2 diabetes. However, the specific compounds and mechanisms responsible for this effect are not known. The aim of this study was to determine the effects of a decaffeinated coffee extract and a synthetic quinide, representative of those found in roasted coffee, 3,4-diferuloyl-l,5-quinolactone, on insulin-stimulated glucose disposal and muscle glucose uptake. Experiments were performed on conscious rats during hyperinsulinemic, euglycemic clamps receiving gastric infusions of saline, a decaffeinated coffee extract (DECAF) (220 mg/kg), or 3,4-diferuloyl-l,5-quinide (DIFEQ) (110 mg/kg). Following treatment, rats received an intravenous bolus of deoxy-[2[-sup.3.H] glucose to assess muscle glucose uptake ([R.sub.g], [mu]mol * [100g.sup.-1] 7 * [min.sup.-1]). Glucose infusions [mg/(kg * min)] required to maintain euglycemia during the tracer period were higher with DIFEQ (14.6 [+ or -] 0.7) than with saline (10.8 [+ or -] 0.7) and DECAF (11.5 [+ or -] 1.1). Despite increased glucose requirements, [R.sub.g] in skeletal (soleus, gastrocnemius, superficial vastus lateralis) and cardiac muscle were unchanged. DECAF or DIFEQ did not affect heart rate, blood pressure, plasma nonesterified fatty acids or liver aminotransferase activity. These results demonstrate that DIFEQ increases whole-body glucose disposal independently of skeletal muscle [R.sub.g]. KEY WORDS: * skeletal muscle glucose uptake * chlorogenic acid * diabetes * metabolism

Six males were required to perform moderate leg extensor exercise for 10 min and then intense exercise until exhaustion to examine the relationship between tricarboxylic acid cycle (TCA) intermediate (TCAI) pool size, TCA cycle flux and pyruvate dehydrogenase activity in human skeletal muscle. It was observed that the TCA cycle flux can greatly increase even if there is a relatively small change in the TCAI pool size. The finding suggests that the imbalance between the rate of pyruvate production and the rate of oxidation in the TCA cycle causes the increase in TCAI during exercise.

The levels of tricarboxylic acid cycle intermediates (TACI) from eight healthy human males were analyzed to determine the effects of prolonged exercise on TCA cycle pool expansion. TCAI concentrations in the skeletal muscle of human subjects exhibited peak expansion within five minutes of submaximal exercise with a rate of expansion that is higher than rodent skeletal muscles. Furthermore, the magnitude of TCAI intermediates in humans was not uniform during exercise.

The effects carbohydrate and branched-chain amino acid (BCAA) availability on the activity of branched-chain oxoacid dehydrogenase (BCOAD) was analyzed during prolonged exercise in healthy individuals. Analysis of muscle metabolism during prolonged exercise indicated the role of low glycogen concentration in increasing the levels of BCOAD in active state. Furthermore, muscle endurance was not enhanced by BCAA supplementation during low-carbohydrate conditions.