Glucose autoregulation is the dominant component of the hormone-independent counterregulatory response to hypoglycemia in the conscious dog.

The contribution of hormone-independent counterregulatory signals in defense of insulin-induced hypoglycemia was determined in adrenalectomized, overnight-fasted conscious dogs receiving hepatic portal vein insulin infusions at a rate 20-fold basal. Either euglycemia was maintained (group 1) or hypoglycemia (≈45 mg/dl) was allowed to occur. There were three hypoglycemic groups: one in which hepatic autoregulation against hypoglycemia occurred in the absence of sympathetic nervous system input (group 2), one in which autoregulation occurred in the presence of norepinephrine (NE) signaling to fat and muscle (group 3), and one in which autoregulation occurred in the presence of NE signaling to fat, muscle, and liver (group 4). Average net hepatic glucose balance (NHGB) during the last hour for groups 1-4 was -0.7 ± 0.1, 0.3 ± 0.1 (P < 0.01 vs. group 1), 0.7 ± 0.1 (P = 0.01 vs. group 2), and 0.8 ± 0.1 (P = 0.7 vs. group 3) mg·kg-1·min-1, respectively. Hypoglycemia per se (group 2) increased NHGB by causing an inhibition of net hepatic glycogen synthesis. NE signaling to fat and muscle (group 3) increased NHGB further by mobilizing gluconeogenic precursors resulting in a rise in gluconeogenesis. Lowering glucose per se decreased nonhepatic glucose uptake by 8.9 mg·kg-1·min-1, and the addition of increased neural efferent signaling to muscle and fat blocked glucose uptake further by 3.2 mg·kg-1·min-1 The addition of increased neural efferent input to liver did not affect NHGB or nonhepatic glucose uptake significantly. In conclusion, even in the absence of increases in counterregulatory hormones, the body can defend itself against hypoglycemia using glucose autoregulation and increased neural efferent signaling, both of which stimulate hepatic glucose production and limit glucose utilization.

Insulin Delivery Into the Peripheral Circulation: A Key Contributor to Hypoglycemia in Type 1 Diabetes.

Hypoglycemia limits optimal glycemic control in type 1 diabetes mellitus (T1DM), making novel strategies to mitigate it desirable. We hypothesized that portal (Po) vein insulin delivery would lessen hypoglycemia. In the conscious dog, insulin was infused into the hepatic Po vein or a peripheral (Pe) vein at a rate four times of basal. In protocol 1, a full counterregulatory response was allowed, whereas in protocol 2, glucagon was fixed at basal, mimicking the diminished α-cell response to hypoglycemia seen in T1DM. In protocol 1, glucose fell faster with Pe insulin than with Po insulin, reaching 56 ± 3 vs. 70 ± 6 mg/dL (P = 0.04) at 60 min. The change in area under the curve (ΔAUC) for glucagon was similar between Pe and Po, but the peak occurred earlier in Pe. The ΔAUC for epinephrine was greater with Pe than with Po (67 ± 17 vs. 36 ± 14 ng/mL/180 min). In protocol 2, glucose also fell more rapidly than in protocol 1 and fell faster in Pe than in Po, reaching 41 ± 3 vs. 67 ± 2 mg/dL (P < 0.01) by 60 min. Without a rise in glucagon, the epinephrine responses were much larger (ΔAUC of 204 ± 22 for Pe vs. 96 ± 29 ng/mL/180 min for Po). In summary, Pe insulin delivery exacerbates hypoglycemia, particularly in the presence of a diminished glucagon response. Po vein insulin delivery, or strategies that mimic it (i.e., liver-preferential insulin analogs), should therefore lessen hypoglycemia.

Effect of knee position on quadriceps muscle force steadiness and activation strategies.

INTRODUCTION: In this study we investigated the effect of knee position on quadriceps force steadiness and activation strategies. METHODS: Quadriceps force steadiness was evaluated in 22 volunteers at two knee positions by testing their ability to regulate submaximal force. Muscle activation strategies were studied in both time and frequency domains using surface electromyography. RESULTS: Quadriceps force fluctuations and the associated agonist and antagonist activity were significantly higher at 90° than at 30° of flexion (P < 0.05). The quadriceps median frequency recorded at 30° was significantly higher than at 90° of flexion (P < 0.05). Regression analyses revealed that force steadiness was related to quadriceps activation and median frequency (P < 0.001), but not to hamstring coactivation (P > 0.05). CONCLUSIONS: The results indicate that knee position significantly affects quadriceps force steadiness and activation strategies. This finding may have important implications for designing a force control testing protocol and interpreting test results.

Rehabilitation of syndesmotic (high) ankle sprains.

CONTEXT: High ankle sprains are common in athletes who play contact sports. Most high ankle sprains are treated nonsurgically with a rehabilitation program. EVIDENCE ACQUISITION: All years of PUBMED, Cochrane Database of Systematic Reviews, CINAHL PLUS, SPORTDiscuss, Google Scholar, and Web of Science were searched to August 2010, cross-referencing existing publications. Keywords included syndesmosis ankle sprain or high ankle sprain and the following terms: rehabilitation, treatment, cryotherapy, braces, orthosis, therapeutic modalities, joint mobilization, massage, pain, pain medications, TENS (ie, transcutaneous electric nerve stimulation), acupuncture, aquatic therapy, strength, neuromuscular training, perturbation training, and outcomes. RESULTS: Level of evidence, 5. A 3-phase rehabilitation program is described. The acute phase is directed at protecting the joint while minimizing pain, inflammation, muscle weakness, and loss of motion. Most patients are treated with some form of immobilization and have weightbearing restrictions. A range of therapeutic modalities are used to minimize pain and inflammation. Gentle mobilization and resistance exercises are used to gain mobility and maintain muscle size and strength. The subacute phase is directed at normalizing range of motion, strength, and function in activities of daily living. Progressive mobilization and strengthening are hallmarks of this phase. Neuromuscular training is begun and becomes the central component of rehabilitation. The advanced training phase focuses on preparing the patient for return to sports participation. Perturbation of support surfaces, agility drills, plyometrics, and sport-specific training are central components of this phase. CONCLUSION: The rehabilitation guidelines discussed may assist clinicians in managing syndesmotic ankle sprains.

Torque-based triggering improves stimulus timing precision in activation tests.

The aim of this study was to assess whether automated torque-based stimulator triggering could improve precision in delivering stimuli near peak torque during voluntary activation tests. The quadriceps activation test was used as a test model in 11 volunteers. Automated torque-based triggering reduced stimulus delivery timing errors by 75% when compared with conventional automated time-based triggering. Torque-based stimulator triggering is recommended as an alternative to automated time-based triggering in voluntary activation tests, as it improves stimulus timing precision and thereby reduces measurement error.