Effect of 24 hours of starvation on plasma glucose and insulin concentrations in subjects with untreated non—insulin-dependent diabetes mellitus

Gannon, Mary C.; Nuttall, Frank Q.; Lane, James T.; Fang, Sean; Gupta, Vishwas; Sandhofer, Charles R.

doi:10.1016/s0026-0495(96)90225-5

Cited by 26 publications

(20 citation statements)

References 30 publications

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“…The reason for the greatly decreased fasting glucose concentration is uncertain but is likely to be the consequence of a reduced store of glycogen and thus a decrease in glycogenolysis rate (5,6,15). A priori, there is no reason to suspect that the LoBAG diet would result in a decreased rate of gluconeogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Effect of a High-Protein, Low-Carbohydrate Diet on Blood Glucose Control in People With Type 2 Diabetes

2004

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There has been interest in the effect of various types and amounts of dietary carbohydrates and proteins on blood glucose. On the basis of our previous data, we designed a high-protein/low-carbohydrate, weight-maintaining, nonketogenic diet. Its effect on glucose control in people with untreated type 2 diabetes was determined. We refer to this as a low-biologically-availableglucose (LoBAG) diet. Eight men were studied using a randomized 5-week crossover design with a 5-week washout period. The carbohydrate:protein:fat ratio of the control diet was 55:15:30. The test diet ratio was 20:30:50. Plasma and urinary ␤-hydroxybutyrate were similar on both diets. The mean 24-h integrated serum glucose at the end of the control and LoBAG diets was 198 and 126 mg/dl, respectively. The percentage of glycohemoglobin was 9.8 ؎ 0.5 and 7.6 ؎ 0.3, respectively. It was still decreasing at the end of the LoBAG diet. Thus, the final calculated glycohemoglobin was estimated to be ϳ6.3-5.4%. Serum insulin was decreased, and plasma glucagon was increased. Serum cholesterol was unchanged. Thus, a LoBAG diet ingested for 5 weeks dramatically reduced the circulating glucose concentration in people with untreated type 2 diabetes. Potentially, this could be a patient-empowering way to ameliorate hyperglycemia without pharmacological intervention. The long-term effects of such a diet remain to be determined. Diabetes 53:2375-2382, 2004 D ata obtained in our laboratory (1-3) as well as from others (reviewed in 4) indicate that glucose that is absorbed after the digestion of glucose-containing foods is largely responsible for the rise in the circulating glucose concentration after ingestion of mixed meals. Dietary proteins, fats, and absorbed fructose and galactose resulting from the digestion of sucrose and lactose, respectively, have little effect on blood glucose concentration.We and others also have reported that even short-term starvation (hours) results in a dramatic decrease in the blood glucose concentration in people with type 2 diabetes (5). This seems to be due largely to a rapid, progressive decrease in the rate of glycogenolysis (5,6). Hepatic glycogen stores in turn are dependent on the content of carbohydrate in the diet (6). Thus, a reduced-carbohydrate diet should result in a lower overnight fasting glucose concentration.To test the hypothesis that a diet that is low in carbohydrate and particularly low in food-derived glucose could lower both the fasting and the postprandial blood glucose in people with type 2 diabetes, we designed a lowcarbohydrate diet in which readily digestible starch-containing foods have been de-emphasized. However, the carbohydrate content is sufficient to prevent ketosis. This is in contrast to the low-carbohydrate diets being advocated for weight loss (7). We refer to this as a lowbiologically-available-glucose (LoBAG) diet. In our study, we also attempted to ensure weight stability. The effect of 5 weeks of this diet on percentage glycohemoglobin and 24-h glucose, insulin, C-peptide, ␤-hydroxybuty...

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Section: Discussionmentioning

confidence: 99%

“…This seems to be due largely to a rapid, progressive decrease in the rate of glycogenolysis (5,6). Hepatic glycogen stores in turn are dependent on the content of carbohydrate in the diet (6).…”

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Effect of a High-Protein, Low-Carbohydrate Diet on Blood Glucose Control in People With Type 2 Diabetes

2004

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“…35 The observed reduction of plasma glucagon after 24 h fasting is, however, at variance with a previous study in which we observed a 22% increase in plasma glucagon after overnight fasting in mice in conjunction with similar level of glycaemia as in the present study. 42 The glucagon response to fasting is not well understood because both increased, 43 decreased 44,45 and unaffected 46 levels have been reported in humans. Whether these discrepancies in glucagon responses to energy restriction result from different lengths of fasting, different antibodies for the determination of glucagon (some antibodies cross react with immunoglobulins, 47 ) or other conditions, deserves to be studied in more detail.…”

Section: Discussionmentioning

confidence: 99%

Leptin increases circulating glucose, insulin and glucagon via sympathetic neural activation in fasted mice

Åhrén

Havel

1999

Int J Obes

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OBJECTIVE: A number of recent studies suggest that leptin has effects on glucose metabolism and pancreatic hormone secretion. Therefore, the effect of leptin administration on circulating glucose, insulin and glucagon in fed and fasted mice was investigated. The potential contribution of the sympathetic nervous system to the effects of leptin was also examined. DESIGN: Recombinant human or murine leptin was administered intraperitoneally (300 mgamouse per 12 h over 24 h) to fed or fasted, normal or chemically sympathectomized NMRI mice. Blood samples were collected at baseline and after 24 h. MEASUREMENTS: Plasma concentrations of glucose, insulin and glucagon. RESULTS: In the fed state (n 24), leptin administration did not affect glucose, insulin or glucagon concentrations after 24 h. Fasting (n 24) reduced body weight by 2.2 AE AE 0.4 g, plasma glucose by 3.7 AE AE 0.4 mmolal, plasma insulin by 138 AE AE 35 pmolal, and plasma glucagon by 32 AE AE 7 pgaml. In fasted mice, human leptin (n 24) increased plasma glucose by 1.5 AE AE 0.2 mmolal (P 0.041), plasma insulin by 95 AE AE 22 pmolal (P 0.018), and plasma glucagon by 16 AE AE 3 pgaml (P 0.025), relative to saline-injected control animals. Murine leptin exerted similar stimulating effects on circulating glucose ( 1.0 AE AE 0.2 mmolal, P 0.046), insulin ( 58 AE AE 17 pmolal, P 0.038) and glucagon ( 24 AE AE 9 pgaml, P 0.018) as human leptin in fasted mice (n 12) with no signi®cant effect in fed mice (n 12). Human leptin did not affect circulating glucose, insulin or glucagon in fasted mice after chemical sympathectomy with 6-hydroxydopamine (40 mgakg iv 48 h prior to fasting; n 12). CONCLUSION: Leptin increases circulating glucose, insulin and glucagon in 24 h fasted mice by a mechanism requiring intact sympathetic nerves.

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“…Despite increased serum glucose level in people with type 2 diabetes, phosphorylase-mediated glycogenolysis continues to contribute ϳ40-50% of overnight glucose production, inappropriately maintaining hyperglycemia (3,4,21,63, 68). Once glycogenolysis decreases, as with extended fasting, the blood glucose concentration decreases dramatically (3,20,24,32, 68). Therefore, understanding how phosphorylase-mediated glycogenolysis is regulated in people with or without diabetes is of considerable importance.…”

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Integrated effects of multiple modulators on human liver glycogen phosphorylasea

Ercan-Fang

Gannon

Rath

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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Hepatic glucose production is increased in people with type 2 diabetes. Glucose released from storage in liver glycogen by phosphorylase accounts for ϳ50% of the glucose produced after an overnight fast. Therefore, understanding how glycogenolysis in the liver is regulated is of great importance. Toward this goal, we have determined the kinetic characteristics of recombinant human liver glycogen phosphorylase a (HLGPa) (active form) and compared them with those of the purified rat enzyme (RLGPa). The Michaelis-Menten constant (K m) of HLGPa for Pi, 5 mM, was about fivefold greater than the Km of RLGPa. Two Pi (substrate) concentrations were used (1 and 5 mM) to cover the physiological range for P i. Other effectors were added at estimated intracellular concentrations. When added individually, AMP stimulated, whereas ADP, ATP and glucose inhibited, activity. These results were similar to those of the RLGPa. However, glucose inhibition was about twofold more potent with the human enzyme. UDP-glucose, glucose 6-phosphate, and fructose 1-phosphate were only minor inhibitors of both enzymes. We reported previously that when all known effectors were present in combination at physiological concentrations, the net effect was no change in RLGPa activity. However, the same combination reduced HLGPa activity, and the inhibition was glucose dependent. We conclude that a combination of the known effectors of phosphorylase a activity, when present at estimated intracellular concentrations, is inhibitory. Of these effectors, only glucose changes greatly in vivo. Thus it may be the major regulator of HLGPa activity. glucose; glycogen metabolism; enzyme regulation; adenosine 5Ј-monophosphate; adenosine 5Ј-diphosphate; adenosine 5Ј-triphosphate; glucose 1-phosphate; fructose 1-phosphate; uridine 5Ј-diphosphate-glucose IN HUMANS, GLUCOSE RELEASED from liver glycogen by the enzyme phosphorylase accounts for ϳ50% of the total glucose produced after an overnight fast, significantly contributing to the maintenance of a normal blood glucose concentration (11,27,38,53,63). Despite increased serum glucose level in people with type 2 diabetes, phosphorylase-mediated glycogenolysis continues to contribute ϳ40-50% of overnight glucose production, inappropriately maintaining hyperglycemia (3,4,21,63, 68). Once glycogenolysis decreases, as with extended fasting, the blood glucose concentration decreases dramatically (3,20,24,32, 68). Therefore, understanding how phosphorylase-mediated glycogenolysis is regulated in people with or without diabetes is of considerable importance.Phosphorylase removes glycosyl units from the terminal branches of glycogen through phosphorolysis, forming glucose 1-phosphate. It is present in two interconvertible forms, phosphorylase a (phosphorylated) and b (unphosphorylated). The a form is the active form. Regulation of phosphorylase is incompletely understood. Phosphorylase has been postulated to be primarily regulated by the interconversion of the active, phosphorylated (phosphorylase a) and inactive, nonphospho...

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Effect of 24 hours of starvation on plasma glucose and insulin concentrations in subjects with untreated non—insulin-dependent diabetes mellitus

Cited by 26 publications

References 30 publications

Effect of a High-Protein, Low-Carbohydrate Diet on Blood Glucose Control in People With Type 2 Diabetes

Effect of a High-Protein, Low-Carbohydrate Diet on Blood Glucose Control in People With Type 2 Diabetes

Leptin increases circulating glucose, insulin and glucagon via sympathetic neural activation in fasted mice

Integrated effects of multiple modulators on human liver glycogen phosphorylasea

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