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PubMed1987

Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics.

Elevated rates of basal hepatic glucose output (bHGO) are significantly correlated with the fasting serum glucose (FSG) level in subjects with non-insulin-dependent diabetes mellitus (NIDDM). This observation suggests that bHGO is a major determinant of the severity of the diabetic state in these subjects. In addition, basal glucagon levels (bGL) are higher in these diabetics than in control subjects, despite the concurrent basal hyperglycemia and hyperinsulinemia, two factors known to suppress glucagon secretion. Although bGL is responsible for sustaining two-thirds of bHGO in normal humans, its role in sustaining elevated rates of bHGO in NIDDM has not been previously defined. To this end, we have studied 13 normal and 10 NIDDM subjects; mean FSG levels were 90 +/- 2 and 262 +/- 21 mg/dl, respectively (P less than .001). The mean fasting serum insulin and glucagon levels were higher in the diabetics than in the controls: 17 +/- 2 vs. 9 +/- 1 microU/ml (P less than .01) and 208 +/- 37 vs. 104 +/- 15 pg/ml (P less than .01), respectively. On separate days, HGO was assessed isotopically (with 3-[3H]glucose) in the basal state and during infusion of somatostatin (SRIF) (600 micrograms/h) alone and in conjunction with replacement infusions of glucose and insulin. The results demonstrate that bHGO is higher in diabetics than in controls (145 +/- 12 vs. 89 +/- 3 mg X m-2 X min-1, P less than .01); during infusion of SRIF alone, HGO was suppressed by 25% (P less than .05) and 34% (P less than .05) of the basal value in controls and diabetics, respectively; when the studies were repeated with glucose levels held constant at or near the FSG level by the glucose-clamp technique, the pattern and degree of HGO suppression was similar to that obtained by infusion of SRIF alone; during isolated glucagon deficiency (SRIF + insulin, 5 mU X m-2 min-1, with serum glucose maintained at basal level), HGO was suppressed by 71 +/- 8% of the basal value in controls (P less than .001) and by 58 +/- 7% in diabetics (P less than .001); and when isolated glucagon deficiency with similar hyperglycemia was created in control subjects, HGO was suppressed by 87% of the basal value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Rates of noninsulin-mediated glucose uptake are elevated in type II diabetic subjects.

Although insulin is extremely potent in regulating glucose transport in insulin-sensitive tissues, all tissues are capable of taking up glucose by facilitated diffusion by means of a noninsulin-mediated glucose uptake (NIMGU) system. Several reports have estimated that in the postabsorptive state the majority of glucose disposal occurs via a NIMGU mechanism. However, these estimates have been either derived or extrapolated in normal humans. In the present study we have directly measured NIMGU rates in 11 normal (C) and 7 Type II noninsulin-dependent diabetic subjects (NIDDM; mean +/- SE fasting serum glucose, 249 +/- 24 mg/dl). To accomplish this, the serum glucose was clamped at a desired level during a period of insulin deficiency induced by a somatostatin infusion (SRIF, 550 micrograms/h). With a concomitant [3-3H]glucose infusion, we could isotopically quantitate glucose disposal rates (Rd) during basal (basal insulin present) and insulin-deficient (SRIF) conditions. With this approach we found that (a) basal Rd was greater in NIDDM than in C, 274 +/- 31 vs. 150 +/- 7 mg/min, due to elevated hepatic glucose output, (b) NIMGU composes 75 +/- 5% of basal Rd in C and 71 +/- 4% in NIDDM, (c) NIDDMS have absolute basal NIMGU rates that are twice that of C (195 +/- 23 vs. 113 +/- 8 mg/min, P less than 0.05), (d) when C were studied under conditions of insulin deficiency (SRIF infusion) and at a serum glucose level comparable to that of the NIDDM group (250 mg/dl), their rates of NIMGU were the same as that of the NIDDM group (186 +/- 19 vs. 195 +/- 23 mg/min; NS). We conclude that (a) in the postabsorptive state, NIMGU is the major pathway for glucose disposal for both C and NIDDM; (b) for a given glucose level the efficiency of NIMGU (NIMGU divided by serum glucose level) is equal in C and NIDDM, but since basal Rd is elevated in NIDDMs their absolute basal rates of NIMGU are higher; and (c) elevated basal rates of NIMGU in NIDDM may play a role in the pathogenesis of the late complications of diabetes.

Adult↗